Visual EMDR stimulation mitigates acute varied stress effects on morphology of hippocampal neurons in male Wistar rats.

Introduction: Stress is a pervasive health concern known to induce physiological changes, particularly impacting the vulnerable hippocampus and the morphological integrity of its main residing cells, the hippocampal neurons. Eye Movement Desensitization and Reprocessing (EMDR), initially developed to alleviate emotional distress, has emerged as a potential therapeutic/preventive intervention for other stress-related disorders. This study aimed to investigate the impact of Acute Variable Stress (AVS) on hippocampal neurons and the potential protective effects of EMDR. Methods: Rats were exposed to diverse stressors for 7 days, followed by dendritic morphology assessment of hippocampal neurons using Golgi-Cox staining. Results: AVS resulted in significant dendritic atrophy, evidenced by reduced dendritic branches and length. In contrast, rats receiving EMDR treatment alongside stress exposure exhibited preserved dendritic morphology comparable to controls, suggesting EMDR's protective role against stressinduced dendritic remodeling. Conclusions: These findings highlight the potential of EMDR as a neuroprotective intervention in mitigating stress-related hippocampal alterations.

K252a Prevents Microglial Activation Induced by Anoxic Stimulation of Carotid Bodies in Rats.

Inducing carotid body anoxia through the administration of cyanide can result in oxygen deprivation. The lack of oxygen activates cellular responses in specific regions of the central nervous system, including the Nucleus Tractus Solitarius, hypothalamus, hippocampus, and amygdala, which are regulated by afferent pathways from chemosensitive receptors. These receptors are modulated by the brain-derived neurotrophic factor receptor TrkB. Oxygen deprivation can cause neuroinflammation in the brain regions that are activated by the afferent pathways from the chemosensitive carotid body. To investigate how microglia, a type of immune cell in the brain, respond to an anoxic environment resulting from the administration of NaCN, we studied the effects of blocking the TrkB receptor on this cell-type response. Male Wistar rats were anesthetized, and a dose of NaCN was injected into their carotid sinus to induce anoxia. Prior to the anoxic stimulus, the rats were given an intracerebroventricular (icv) infusion of either K252a, a TrkB receptor inhibitor, BDNF, or an artificial cerebrospinal fluid (aCSF). After the anoxic stimulus, the rats were perfused with paraformaldehyde, and their brains were processed for microglia immunohistochemistry. The results indicated that the anoxic stimulation caused an increase in the number of reactive microglial cells in the hypothalamic arcuate, basolateral amygdala, and dentate gyrus of the hippocampus. However, the infusion of the K252a TrkB receptor inhibitor prevented microglial activation in these regions.

Acoustic Stress Induces Opposite Proliferative/Transformative Effects in Hippocampal Glia.

The hippocampus is a brain region crucially involved in regulating stress responses and highly sensitive to environmental changes, with elevated proliferative and adaptive activity of neurons and glial cells. Despite the prevalence of environmental noise as a stressor, its effects on hippocampal cytoarchitecture remain largely unknown. In this study, we aimed to investigate the impact of acoustic stress on hippocampal proliferation and glial cytoarchitecture in adult male rats, using environmental noise as a stress model. After 21 days of noise exposure, our results showed abnormal cellular proliferation in the hippocampus, with an inverse effect on the proliferation ratios of astrocytes and microglia. Both cell lineages also displayed atrophic morphologies with fewer processes and lower densities in the noise-stressed animals. Our findings suggest that, stress not only affects neurogenesis and neuronal death in the hippocampus, but also the proliferation ratio, cell density, and morphology of glial cells, potentially triggering an inflammatory-like response that compromises their homeostatic and repair functions.

Vitamin D Receptor (VDR) Genetic Variants: Relationship of FokI Genotypes with VDR Expression and Clinical Disease Activity in Systemic Lupus Erythematosus Patients.

Vitamin D (VD) deficiency is more frequent in systemic lupus erythematosus (SLE) patients than in control subjects (CS); genetic variants in the VD receptor (VDR) could contribute to the clinical disease activity. This study was aimed to determine the association of the VDR variants FokI (rs2228570), BsmI (rs1544410), ApaI (rs7975232), and TaqI (rs731236) with susceptibility to the disease, VD status, VDR mRNA expression, and clinical disease activity in SLE patients. A cross-sectional study was conducted in 194 SLE and 196 CS Mexican women. Immunoassays quantified serum calcidiol and calcitriol. Genotyping was performed by allelic discrimination assays and mRNA VDR expression by qPCR. The FokI variant was not in linkage disequilibrium with BsmI, ApaI, and TaqI VDR variants. SLE patient carriers of the TT FokI genotype showed higher clinical disease activity scores. Notably, the mRNA VDR expression was higher in SLE patients vs. CS, in active vs. inactive SLE patients, and in participants of both study groups with vitamin D deficiency, higher calcitriol levels, and TT FokI genotype carriers. In conclusion, the TT FokI VDR genotype was related to high VDR expression and clinical disease activity in systemic lupus erythematosus patients.

Immediate Early Gene c-fos in the Brain: Focus on Glial Cells.

The c-fos gene was first described as a proto-oncogene responsible for the induction of bone tumors. A few decades ago, activation of the protein product c-fos was reported in the brain after seizures and other noxious stimuli. Since then, multiple studies have used c-fos as a brain activity marker. Although it has been attributed to neurons, growing evidence demonstrates that c-fos expression in the brain may also include glial cells. In this review, we collect data showing that glial cells also express this proto-oncogene. We present evidence demonstrating that at least astrocytes, oligodendrocytes, and microglia express this immediate early gene (IEG). Unlike neurons, whose expression changes used to be associated with depolarization, glial cells seem to express the c-fos proto-oncogene under the influence of proliferation, differentiation, growth, inflammation, repair, damage, plasticity, and other conditions. The collected evidence provides a complementary view of c-fos as an activity marker and urges the introduction of the glial cell perspective into brain activity studies. This glial cell view may provide additional information related to the brain microenvironment that is difficult to obtain from the isolated neuron paradigm. Thus, it is highly recommended that detection techniques are improved in order to better differentiate the phenotypes expressing c-fos in the brain and to elucidate the specific roles of c-fos expression in glial cells.

Impact of transplantation on neutrophil extracellular trap formation in patients with end-stage renal disease: A single-center, prospective cohort study.

ABSTRACT: Increased neutrophil extracellular trap (NET) formation associates with high cardiovascular risk and mortality in patients with end-stage renal disease (ESRD). However, the effect of transplantation on NETs and its associated markers remains unclear. This study aimed to characterize circulating citrullinated Histone H3 (H3cit) and Peptidyl Arginase Deiminase 4 (PAD4) in ESRD patients undergoing transplantation and evaluate the ability of their neutrophils to release NETs.This prospective cohort study included 80 healthy donors and 105 ESRD patients, out of which 95 received a transplant. H3cit and PAD4 circulating concentration was determined by enzyme-linked immunosorbent assay in healthy donors and ESRD patients at the time of enrollment. An additional measurement was carried out within the first 6 months after transplant surgery. In vitro NET formation assays were performed in neutrophils isolated from healthy donors, ESRD patients, and transplant recipients.H3cit and PAD4 levels were significantly higher in ESRD patients (H3cit, 14.38 ng/mL [5.78-27.13]; PAD4, 3.22 ng/mL [1.21-6.82]) than healthy donors (H3cit, 6.45 ng/mL [3.30-11.65], P < .0001; PAD4, 2.0 ng/mL [0.90-3.18], P = .0076). H3cit, but not PAD4, increased after transplantation, with 44.2% of post-transplant patients exhibiting high levels (≥ 27.1 ng/mL). In contrast, NET release triggered by phorbol 12-myristate 13-acetate was higher in neutrophils from ESRD patients (70.0% [52.7-94.6]) than healthy donors (32.2% [24.9-54.9], P < .001) and transplant recipients (19.5% [3.5-65.7], P < .05).The restoration of renal function due to transplantation could not reduce circulating levels of H3cit and PAD4 in ESRD patients. Furthermore, circulating H3cit levels were significantly increased after transplantation. Neutrophils from transplant recipients exhibit a reduced ability to form NETs.

Presence of Adenovirus-36 DNA in Adipose Tissue of Women: Relationship with Adipocyte Morphology and the Expression of C/EBPß and HIF-1α.

BACKGROUND: Human adenovirus 36 (HAd36) infection has been associated with obesity. Experiments using 3T3-L1 adipocyte cultured cells and human adipose stem cells (hASCc) have shown that HAd36 stimulates the expression of genes implicated in cell differentiation and increased lipid accumulation. The presence of HAd36 in adipose tissue of overweight and obese women has also been confirmed. This study aims to analyze the presence of HAd36 DNA in the adipose tissue of women undergoing surgery for weight reduction and its relationship with obesity through changes in adipocyte morphology as well as the expression of C/EBPß and HIF-1α. METHODS: Fifty-two subcutaneous adipose tissue biopsies were collected. The anthropometric parameters measured were weight, height, skin folds, body circumferences, and body fat percentage. Biochemical measures were performed for glucose, cholesterol, triglycerides, cholesterol HDL-c, and LDL-c. The presence of HAd36 DNA was performed by conventional PCR. Adipocyte morphology was analyzed in H&E-stained sections using ImageJ/Fiji software. The expression of genes C/EBPß, HIF-1α and ß-actin was determined using TaqMan probes. RESULTS: HAd36 DNA was detected in 31% of adipose tissue samples. The presence of viral DNA was not significantly associated with anthropometric, clinical, or metabolic measurements, or with changes in adipose tissue morphology. The levels of mRNA expression for C/EBPß and HIF-1α did not show significant differences between positive and negative samples for HAd36 (p>0.05). CONCLUSION: The presence of HAd36 DNA in adipose tissue was identified, but it was not related to morphological changes of adipocytes, or the expression of C/EBPß and HIF-1α. Further studies are needed to confirm these findings.

Melatonin modifies SOX2+ cell proliferation in dentate gyrus and modulates SIRT1 and MECP2 in long-term sleep deprivation.

Melatonin is a pleiotropic molecule that, after a short-term sleep deprivation, promotes the proliferation of neural stem cells in the adult hippocampus. However, this effect has not been observed in long-term sleep deprivation. The precise mechanism exerted by melatonin on the modulation of neural stem cells is not entirely elucidated, but evidence indicates that epigenetic regulators may be involved in this process. In this study, we investigated the effect of melatonin treatment during a 96-hour sleep deprivation and analyzed the expression of epigenetic modulators predicted by computational text mining and keyword clusterization. Our results showed that the administration of melatonin under sleep-deprived conditions increased the MECP2 expression and reduced the SIRT1 expression in the dentate gyrus. We observed that let-7b, mir-132, and mir-124 were highly expressed in the dentate gyrus after melatonin administration, but they were not modified by sleep deprivation. In addition, we found more Sox2+/5-bromo-2'-deoxyuridine (BrdU)+ cells in the subgranular zone of the sleep-deprived group treated with melatonin than in the untreated group. These findings may support the notion that melatonin modifies the expression of epigenetic mediators that, in turn, regulate the proliferation of neural progenitor cells in the adult dentate gyrus under long-term sleep-deprived conditions. All procedures performed in this study were approved by the Animal Ethics Committee of the University of Guadalajara, Mexico (approval No. CI-16610) on January 2, 2016.

Male rats exhibit higher pro-BDNF, c-Fos and dendritic tree changes after chronic acoustic stress.

Prolonged or intense exposure to environmental noise (EN) has been associated with a number of changes in auditory organs as well as other brain structures. Notably, males and females have shown different susceptibilities to acoustic damage as well as different responses to environmental stressors. Rodent models have evidence of sex-specific changes in brain structures involved in noise and sound processing. As a common effect, experimental models have demonstrated that dendrite arborizations reconfigure in response to aversive conditions in several brain regions. Here, we examined the effect of chronic noise on dendritic reorganization and c-Fos expression patterns of both sexes. During 21 days male and female rats were exposed to a rats' audiogram-fitted adaptation of a noisy environment. Golgi-Cox and c-Fos staining were performed at auditory cortices (AC) and hippocampal regions. Sholl analysis and c-Fos counts were conducted for evidence of intersex differences. In addition, pro-BDNF serum levels were also measured. We found different patterns of c-Fos expression in hippocampus and AC. While in AC expression levels showed rapid and intense increases starting at 2 h, hippocampal areas showed slower rises that reached the highest levels at 21 days. Sholl analysis also evidenced regional differences in response to noise. Dendritic trees were reduced after 21 days in hippocampus but not in AC. Meanwhile, pro-BDNF levels augmented after EN exposure. In all analyzed variables, exposed males were the most affected. These findings suggest that noise may exert differential effects on male and female brains and that males could be more vulnerable to the chronic effects of noise.

Male/female Differences in Radial Arm Water Maze Execution After Chronic Exposure to Noise.

INTRODUCTION: Noise is one of the main sources of discomfort in modern societies. It affects physiology, behavior, and cognition of exposed subjects. Although the effects of noise on cognition are well known, gender role in noise-cognition relationship remains controversial. AIM: We analyzed the effects of noise on the ability of male and female rats to execute the Radial Arm Water Maze (RAWM) paradigm. MATERIALS AND METHODS: Male and female Wistar rats were exposed to noise for 3 weeks, and the cognitive effects were assessed at the end of the exposure. RAWM execution included a three-day training phase and a reversal-learning phase conducted on the fourth day. Escape latency, reference memory errors, and working memory errors were quantified and compared between exposed and non-exposed subjects. RESULTS: We found that male rats were in general more affected by noise. Execution during the three-day learning phase evidenced that male exposed rats employed significantly more time to acquire the task than the non-exposed. On the other hand, the exposed females solved the paradigm in latencies similar to control rats. Both, males and females diminished their capacity to execute on the fourth day when re-learning abilities were tested. CONCLUSION: We conclude that male rats might be less tolerable to noise compared to female ones and that spatial learning may be a cognitive function comparably more vulnerable to noise.

Environmental noise exposure modifies astrocyte morphology in hippocampus of young male rats.

BACKGROUND: Chronic exposure to noise induces changes on the central nervous system of exposed animals. Those changes affect not only the auditory system but also other structures indirectly related to audition. The hippocampus of young animals represents a potential target for these effects because of its essential role in individuals' adaptation to environmental challenges. OBJECTIVE: The aim of the present study was to evaluate hippocampus vulnerability, assessing astrocytic morphology in an experimental model of environmental noise (EN) applied to rats in pre-pubescent stage. MATERIALS AND METHODS: Weaned Wistar male rats were subjected to EN adapted to the rats' audiogram for 15 days, 24 h daily. Once completed, plasmatic corticosterone (CORT) concentration was quantified, and immunohistochemistry for glial fibrillary acidic protein was taken in hippocampal DG, CA3, and CA1 subareas. Immunopositive cells and astrocyte arborizations were counted and compared between groups. RESULTS: The rats subjected to noise exhibited enlarged length of astrocytes arborizations in all hippocampal subareas. Those changes were accompanied by a marked rise in serum CORT levels. CONCLUSIONS: These findings confirm hippocampal vulnerability to EN and suggest that glial cells may play an important role in the adaptation of developing the participants to noise exposure.

Nitric oxide in the nucleus of the tractus solitarius is involved in hypoglycemic conditioned response.

The repeated injection of insulin (unconditioned stimulus, UCS) immediately followed by exposure to sensory stimulation (e.g. sound or odor; conditioned stimulus, CS) results in a learned conditioned reflex in which the exposure to the CS alone lowers blood glucose. The brain regions participating in this hypoglycemic Pavlovian response remain unknown. Here we investigate if nitric oxide (NO) in the nucleus tractus solitarius (NTS), a nucleus known to be involved in glucose homeostasis, participates in this hypoglycemic reflex. Insulin injections (UCS) were paired with exposure to menthol odor (CS). After 8-10 reinforcements (4-5days training), rats acquire the learned hypoglycemic response. An increase in c-Fos expression was observed in the NTS, the ventrolateral hypothalamic nucleus (VLH) and other brain regions of conditioned rats. Microinjections of 3-(5'-hydroxymethyl-2'furyl)-1-benzyl indazole (YC-1) a stimulator of soluble guanylate cyclase (sGC) into NTS before the UCS accelerated the acquisition of the learned hypoglycemic response; 5-6 reinforcement produced pronounced glucose drop when exposed to the CS. In contrast, an inhibitor of NO synthase (NOS) Nω-Nitro-l-arginine methyl ester (L-NAME) in the NTS prolonged the required training period (11-15 reinforcements) to obtain the hypoglycemic reflex, and reduced the glycemic response. The number of c-Fos expressing cells in the NTS and VLH in rats receiving YC-1was significantly higher than that observed in rats receiving L-NAME. These findings suggest that NO-cGMP-PKG signaling in the NTS can modify the acquisition of conditioned hypoglycemia, and suggests that this nucleus directly participates in this reflex.

Rapid Eye Movement Sleep Deprivation Produces Long-Term Detrimental Effects in Spatial Memory and Modifies the Cellular Composition of the Subgranular Zone.

Sleep deprivation (SD) affects spatial memory and proliferation in the dentate gyrus. It is unknown whether these deleterious effects persist in the long run. The aim of this study was to evaluate the proliferation, differentiation and maturation of neural progenitors as well as spatial memory 21 days after suffering SD. Sixty-day old male Balb/C mice were exposed to 72-h REM-SD. Spatial memory, cell fate, apoptosis and expression levels of insulin-like growth factor 1 receptor (IGF-1R) were evaluated in the hippocampus at 0, 14, and 21 days after SD or control conditions. After 21-days recovery period, memory performance was assessed with the Barnes maze, we found a significant memory impairment in SD mice vs. control (94.0 ± 10.2 s vs. 25.2 ± 4.5 s; p < 0.001). The number of BrdU+ cells was significantly decreased in the SD groups at day 14 (controls = 1.6 ± 0.1 vs. SD mice = 1.2 ± 0.1 cells/field; p = 0.001) and at day 21 (controls = 0.2 ± 0.03 vs. SD mice = 0.1 ± 0.02 cells/field; p < 0.001). A statistically significant decrease was observed in neuronal differentiation (1.4 ± 0.1 cells/field vs. 0.9 ± 0.1 cells/field, p = 0.003). Apoptosis was significantly increased at day 14 after SD (0.53 ± 0.06 TUNEL+ cells/field) compared to controls (0.19 ± 0.03 TUNEL+ cells/field p < 0.001) and at 21-days after SD (SD mice 0.53 ± 0.15 TUNEL+ cells/field; p = 0.035). At day 0, IGF-1R expression showed a statistically significant reduction in SD animals (64.6 ± 12.2 units) when compared to the control group (102.0 ± 9.8 units; p = 0.043). However, no statistically significant differences were found at days 14 and 21 after SD. In conclusion, a single exposition to SD for 72-h can induce deleterious effects that persist for at least 3 weeks. These changes are characterized by spatial memory impairment, reduction in the number of hippocampal BrdU+ cells and persistent apoptosis rate. In contrast, changes IGF-1R expression appears to be a transient event. Highlight Sleep deprivation affects spatial memory and proliferation in the dentate gyrus. To date it is unknown whether these deleterious effects are persistent over a long period of time. We analyzed the effects of sleep deprivation in the hippocampus after 21 days of recovery sleep. Our findings indicate that after sleep recovery, the detrimental effects of SD can be observed for at least 2 weeks, as shown by a reduction in memory performance, changes in the hippocampal cellular composition and higher apoptotic rate over a long period of time.

Phenytoin enhances the phosphorylation of epidermal growth factor receptor and fibroblast growth factor receptor in the subventricular zone and promotes the proliferation of neural precursor cells and oligodendrocyte differentiation.

Phenytoin is a widely used antiepileptic drug that induces cell proliferation in several tissues, such as heart, bone, skin, oral mucosa and neural precursors. Some of these effects are mediated via fibroblast growth factor receptor (FGFR) and epidermal growth factor receptor (EGFR). These receptors are strongly expressed in the adult ventricular-subventricular zone (V-SVZ), the main neurogenic niche in the adult brain. The aim of this study was to determine the cell lineage and cell fate of V-SVZ neural progenitors expanded by phenytoin, as well as the effects of this drug on EGFR/FGFR phosphorylation. Male BALB/C mice received 10 mg/kg phenytoin by oral cannula for 30 days. We analysed the proliferation of V-SVZ neural progenitors by immunohistochemistry and western blot. Our findings indicate that phenytoin enhanced twofold the phosphorylation of EGFR and FGFR in the V-SVZ, increased the number of bromodeoxyuridine (BrdU)+/Sox2+ and BrdU+/doublecortin+ cells in the V-SVZ, and expanded the population of Olig2-expressing cells around the lateral ventricles. After phenytoin removal, a large number of BrdU+/Receptor interacting protein (RIP)+ cells were observed in the olfactory bulb. In conclusion, phenytoin enhanced the phosphorylation of FGFR and EGFR, and promoted the expression of neural precursor markers in the V-SVZ. In parallel, the number of oligodendrocytes increased significantly after phenytoin removal.

Sex-related effects of sleep deprivation on depressive- and anxiety-like behaviors in mice.

Anxiety and depressive symptoms are generated after paradoxical sleep deprivation (PSD). However, it is not clear whether PSD produces differential effects between females and males. The aim of this study was to assess the effect of PSD on anxiety- and depressive-like behaviors between sexes. Male and female BALB/c mice were divided in three groups: the control group, the 48-h PSD group and the 96-h PSD group. Immediately after PSD protocols, the forced swimming and open field test were applied. Sucrose consumption test was used to evaluate the middle-term effect of PSD. We found that corticosterone serum levels showed significant differences in the 96-h PSD females as compared to 96-h PSD males. In the open-field test, the 48-h and 96-h PSD females spent more time at the periphery of the field, and showed high locomotion as compared to males. In the elevated plus maze, the 48-h PSD females spent more time in closed arms than males, which is compatible with anxiety-like behavior. The forced swim test indicated that the 96-h PSD males spent more time swimming as compared to the 96-h PSD females. Remarkably, the 96-h PSD males had lower sucrose intake than the 96-h PSD females, which suggest that male mice have proclivity to develop a persistent depressive-like behavior late after PSD. In conclusion, male mice showed a significant trend to depressive-like behaviors late after sleep deprivation. Conversely, female have a strong tendency to display anxiety- and depressive-like behaviors immediately after sleep deprivation.

Hippocampal cytogenesis and spatial learning in senile rats exposed to chronic variable stress: effects of previous early life exposure to mild stress.

In this study, we exposed adult rats to chronic variable stress (CVS) and tested the hypothesis that previous early-life exposure to stress changes the manner in which older subjects respond to aversive conditions. To this end, we analyzed the cytogenic changes in the hippocampus and hippocampal-dependent spatial learning performance. The experiments were performed on 18-month-old male rats divided into four groups as follows: Control (old rats under standard laboratory conditions), Early-life stress (ELS; old rats who were exposed to environmental noise from postnatal days, PNDs 21-35), CVS + ELS (old rats exposed to a chronic stress protocol who were previously exposed to the early-life noise stress) and CVS (old rats who were exposed only to the chronic stress protocol). The Morris Water Maze (MWM) was employed to evaluate the spatial learning abilities of the rats at the end of the experiment. Immunohistochemistry against 5'Bromodeoxyuridine (BrdU) and glial fibrillar acidic protein (GFAP) was also conducted in the DG, CA1, CA2 and CA3 regions of the hippocampus. We confocally analyzed the cytogenic (BrdU-labeled cells) and astrogenic (BrdU + GFAP-labeled cells) changes produced by these conditions. Using this procedure, we found that stress diminished the total number of BrdU+ cells over the main proliferative area of the hippocampus (i.e., the dentate gyrus, DG) but increased the astrocyte phenotypes (GFAP + BrdU). The depleted BrdU+ cells were restored when the senile rats also experienced stress at the early stages of life. The MWM assessment demonstrated that stress also impairs the ability of the rats to learn the task. This impairment was not present when the stressful experience was preceded by the early-life exposure. Thus, our results support the idea that previous exposure to mild stressing agents may have beneficial effects on aged subjects.

Early-life exposure to noise reduces mPFC astrocyte numbers and T-maze alternation/discrimination task performance in adult male rats.

In this experiment, we evaluated the long-term effects of noise by assessing both astrocyte changes in medial prefrontal cortex (mPFC) and mPFC-related alternation/discrimination tasks. Twenty-one-day-old male rats were exposed during a period of 15 days to a standardized rats' audiogram-fitted adaptation of a human noisy environment. We measured serum corticosterone (CORT) levels at the end of the exposure and periodically registered body weight gain. In order to evaluate the long-term effects of this exposure, we assessed the rats' performance on the T-maze apparatus 3 months later. Astrocyte numbers and proliferative changes in mPFC were also evaluated at this stage. We found that environmental noise (EN) exposure significantly increased serum CORT levels and negatively affected the body weight gain curve. Accordingly, enduring effects of noise were demonstrated on mPFC. The ability to solve alternation/discrimination tasks was reduced, as well as the number of astroglial cells. We also found reduced cytogenesis among the mPFC areas evaluated. Our results support the idea that early exposure to environmental stressors may have long-lasting consequences affecting complex cognitive processes. These results also suggest that glial changes may become an important element behind the cognitive and morphological alterations accompanying the PFC changes seen in some stress-related pathologies.

Dopamine receptor dysregulation in hippocampus of aged rats underlies chronic pulsatile L-Dopa treatment induced cognitive and emotional alterations.

L-Dopa is the major symptomatic therapy for Parkinson's disease, which commonly occurs in elderly patients. However, the effects of chronic use on mood and cognition in old subjects remain elusive. In order to compare the effects of a chronic pulsatile L-Dopa treatment on emotional and cognitive functions in young (3 months) and old (18 months) intact rats, an L-Dopa/carbidopa treatment was administered every 12 h over 4 weeks. Rats were assessed for behavioural despair (repeated forced swimming test, RFST), anhedonia (sucrose preference test, SPT) and spatial learning (Morris water maze, MWM) in the late phase of treatment (T). Neuronal expression of Fos in the hippocampus at the early and late phases of T, as well as after MWM was studied. The density and ratio of dopamine D5r, D3r and D2r receptors were also evaluated in the hippocampus using immunohistochemistry and confocal microscopy. Young rats showed similar patterns during behavioural tests, whereas aged treated rats showed increased immobility counts in RFST, diminished sucrose liquid intake in SPT, and spatial learning impairment during MWM. Fos expression was significantly blunted in the aged treated group after MWM. The density of D5r, D3r and D2r was increased in both aged groups. The treatment reduced the ratio of D5r/D3r and D5r/D2r in both groups. Moreover, aged treated subjects had significant lower values of D5r/D3r and higher values of D5r/D2r when compared with young treated subjects. These results indicate that chronic L-Dopa treatment in itself could trigger emotional and cognitive dysfunctions in elderly subjects through dopamine receptor dysregulation.

Nitric oxide in the commissural nucleus tractus solitarii regulates carotid chemoreception hyperglycemic reflex and c-Fos expression.

Carotid body chemoreceptors function as glucose sensors and contribute to glucose homeostasis. The nucleus tractus solitarii (NTS) is the first central nervous system (CNS) nuclei for processing of information arising in the carotid body. Here, we microinjected a nitric oxide (NO) donor sodium nitroprusside (SNP), an NO-independent activator of the soluble guanylyl cyclase (sGC) (YC1) or an NO-synthase (NOS) inhibitor Nω-nitro-l-arginine methyl ester (L-NAME) into the commissural NTS (cNTS) before carotid chemoreceptor anoxic stimulation and measured arterial glucose and the expression of Fos-like immunoreactivity (Fos-ir). Male Wistar rats (250-300 g) were anesthetized, and the carotid sinus was vascularly isolated. Either artificial cerebrospinal fluid (aCSF), SNP, YC1 or L-NAME were stereotaxically injected into the cNTS. The SNP and YC1 infused into the cNTS before carotid chemoreceptor stimulation (SNP-2 and YC1-2 groups) similarly increased arterial glucose compared to the aCSF-2 group. By contrast, infusion of L-NAME into the cNTS before carotid chemoreceptor stimulation (L-NAME-2 group) decreased arterial glucose concentration. The number of cNTS Fos-ir neurons, determined in all the groups studied except for YC1 groups, significantly increased in SNP-2 rat when compared to the aCSF-2 or SNP-2 groups. Our findings demonstrate that NO signaling, and the correlative activation of groups of cNTS neurons, plays key roles in the hyperglycemic reflex initiated by carotid chemoreceptor stimulation.