Effect of intra-hippocampal injection of human recombinant growth hormone on synaptic plasticity in the nucleus basalis magnocellularis-lesioned aged rats / Efeito da injeção intrahipocampal de hormônio do crescimento humano recombinante sobre a plasticidade sináptica em ratos envelhecidos lesados do núcleo basalis magnocellularis

ABSTRACT In this study, we proposed that administration of hippocampal growth hormone in ageing animals with growth hormone deficiency can compensate long-term potentiation and synaptic plasticity in nucleus basalis magnocellularis (NBM)-lesioned rats. Aged male Wistar rats were randomly divided into six groups (seven in each) of sham-operated healthy rats (Cont); NBM-lesioned rats (L); NBM-lesioned rats and intrahippocampal injection of growth hormone vehicle (L + Veh); NBM-lesioned and intrahippocampal injection of growth hormone (10, 20 and 40 µg.2 µl-1) (L + GH). In vivo electrophysiological recording techniques were used to characterize maintenance of long-term potentiation at distinct times (1, 2, 3, 24 and 48 hours) after high-frequency stimulation. The population spike was enhanced significantly for about 48 hours following tetanic stimulation in rats treated with a dose-dependent growth hormone compared to the vehicle group (p < 0.05), possibly through neuronal plasticity and neurogenesis in affected areas.

RESUMO Neste estudo, propusemos que a administração de hormônio hipocampal do crescimento em animais envelhecidos com deficiência de hormônio do crescimento pode compensar a potencialização em longo prazo e a plasticidade sináptica em ratos lesados do núcleo basalis magnocellularis (NBM). Ratos machos Wistar foram divididos aleatoriamente em seis grupos (sete ratos em cada grupo) de ratos falso-operados saudáveis (Cont); ratos lesados do NBM (L); ratos lesados do NBM e injeção intrahipocampal de veículo de hormônio do crescimento (L + Veh); ratos lesados do NBM e injeção de hormônio do crescimento (10, 20 e 40 μg.2 μl-1) (L + GH). Técnicas de registro eletrofisiológico in vivo foram utilizadas para caracterizar a manutenção da potencialização em longo prazo em momentos distintos (1, 2, 3, 24 e 48 horas) após estimulação de alta frequência. O pico populacional aumentou significativamente cerca de 48 horas após a estimulação tetânica em ratos tratados com um hormônio do crescimento dose-dependente, em comparação com o grupo veículo (p <0,05), possivelmente através da plasticidade neuronal e da neogênese nas áreas afetadas.

Meynert and the basal nucleus / Meynert e o núcleo basal

Meynert described the "loop of the peduncular foot" (Schlinge des Hirnschenkelfusses), and its ganglion (Ganglion der Hirnschenkelschlinge) and related them to Reil's Substantia innominata and Gratiolet's Ansa peduncularis, from which he apparently built up his findings. Koelliker renamed the ganglion with the eponymous designation Meynert'sches Basalganglion (Meynert's basal ganglion), a name which endures to the present day, and described its topographical spread in relation to neighboring structures. Meynert and Koelliker also described aspects of cell composition of the ganglion (or nucleus) with a better account of the latter. Both, together with Reil and Gratiolet, were the outstanding personalities of the 19th century who performed the pioneering studies on basal formations of the forebrain. After these works, a considerable body of research appeared in the 20th century, with a focus on Meynert's basal nucleus and related structures. The development of further knowledge about these structures revealed their great importance in the activity of the brain, as evidenced in both normal and pathological states.

Meynert descreveu a "alça do pé do pedúnculo" (Schlingedes Hirnschenkelfusses) e seu gânglio (Ganglion der Hirnschenkelschlinge), relacionando-os à Substantia innominata de Reil e à Ansa peduncularis de Gratiolet, a partir dos quais aparentemente desenvolveu seus achados. Koelliker renomeou o gânglio com a designação epônima de Meynert'sches Basalganglion (gânglio basal de Meynert), que perdura até o presente, e descreveu sua extensão topográfica em relação às estruturas vizinhas. Meynert e Koelliker descreveram também aspectos da composição celular do gânglio (ou núcleo), com um relato melhor do segundo. Ambos, juntamente com Reil e Gratiolet, foram as personalidades de destaque do século 19 que realizaram os estudos pioneiros sobre formações basais do prosencéfalo. Após esses, um número considerável de estudos apareceu no século 20, com foco no núcleo basal de Meynert e estruturas relacionadas. O desenvolvimento ulterior do saber sobre as mesmas mostraram sua grande importância na atividade cerebral, como visto em condições normais e patológicas.

effect of treadmill running on passive avoidance learning in animal model of Alzheimer disease

Alzheimer's disease was known as a progressive neurodegenerative disorder in the elderly and is characterized by dementia and severe neuronal loss in the some regions of brain such as nucleus basalis magnocellularis. It plays an important role in the brain functions such as learning and memory. Loss of cholinergic neurons of nucleus basalis magnocellularis by ibotenic acid can commonly be regarded as a suitable model of Alzheimer's disease. Previous studies reported that exercise training may slow down the onset and progression of memory deficit in neurodegenerative disorders. This research investigates the effects of treadmill running on acquisition and retention time of passive avoidance deficits induced by ibotenic acid nucleus basalis magnocellularis lesion. Male Wistar rats were randomly selected and divided into five groups as follows: Control, sham, Alzheimer, exercise before Alzheimer, and exercise groups. Treadmill running had a 21 day period and Alzheimer was induced by 5 micro g/ micro l bilateral injection of ibotenic acid in nucleus basalis magnocellularis. Our results showed that ibotenic acid lesions significantly impaired passive avoidance acquisition [P < 0.01] and retention [P < 0.001] performance, while treadmill running exercise significantly [P < 0.001] improved passive avoidance learning in NBM-lesion rats. Treadmill running has a potential role in the prevention of learning and memory impairments in NBM-lesion rats

Effect of tanshinone IIA on the change of calcium current induced by beta-amyloid protein 25-35 in neurons of nucleus basalis of Meynert / 中南大学学报(医学版)

OBJECTIVE@#To explore the effect of tanshinone IIA (TanIIA) on calcium current induced by beta-amyloid protein 25-35 (Abeta25-35) in neurons of nucleus basalis of Meynert (nbM).@*METHODS@#Cell acute dissociated technique and the whole-cell recording model of patch-clamp technique of single-cell were used. The voltage-dependent calcium current in neurons of nbM was recorded in SD rats first. Then the effect of TanIIA on the voltage-dependent calcium current in the neurons was assayed. The change of calcium current induced by Abeta25-35 as well as the effect of TanIIA on the change of calcium current induced by Abeta25-35 in neurons of nbM were analyzed.@*RESULTS@#Extracellular fluid containing different concentrations of TanIIA was irrigated, respectively. The peak current did not change obviously. There was no difference in current density between the TanIIA group and the control group at 0 mV (P>0.05). Extracellular fluid containing 200 nmol/L Abeta25-35 was irrigated after the normal calcium current recorded under whole patch clamp, and the peak current changed obviously. There was distinct difference in the current density between the Abeta group and the control group at 0 mV (P0.05).@*CONCLUSION@#In vitro, TanIIA could inhibit the calcium current amplification induced by Abeta25-35 in neurons of nbM. TanIIA may protect neurons against the toxicity of Abeta and decrease the inward flow of Ca(2+).

Caracterização dos efeitos da estimulação elétrica no núcleo basalis magnocelular no potencial de campo local e na freqüência cardíaca no condicionamento comportamental de ratos Wistar / Characterization of nucleus basalis magnocelular electrical stimulation effects on local field potential and heart rate in behavioral conditioning Wistar rats

Estudamos os efeitos da estimulação elétrica no nucleus basalis magnocelular (Meynert), núcleo colinégico que projeta aferências para o córtex cerebral e tem sido associado a mecanismos de aprendizagem e memória. Verificamos os efeitos eletrofisiológicos induzidos pela estimulação elétrica do núcleo basalis pareado com apresentação de um tom puro. Caracterizamos a dinâmica da atividade elétrica neural do cortex auditivo primário e de núcleos subcorticais relacionados à circuitaria da aprendizagem e memória, durante o condicionamento auditivo nos momentos de aquisição e de revocação além correlacioná-las a dinâmica de freqüência cardiaca, variável que pode exprimir a relevância de um estímulo...

Acetilcholine is related to learning and memory and is related to cortical activation. We studied the effects electrically stimulating the basal forebrain - the main cholinergic afferent to the cortex, while presenting paired and unpaired pure tones. Mathematical techniques were used to analyze electrophysiological data. The dynamics from primary auditory cortex and related subcortical nuclei were correlated to the auditory conditioning. We also correlated brain activity to the heart dynamics, considered a reliable measure of learning and conditioning, an interesting approach that uncovers the relevance of stimulus that is not detectable through other behavioral variables...

[Effects of intramedial septum infusion of physostigmine on hippocamal EEG and spatial memory in animal model of Alzheimer's disease]

The basalis magnocellularis nucleus [NBM] cholinergic projections to amygdala and forntal cortex have a crucial role in spatial learning and memory. There are relations between septum, hippocampus, amygdala and cerebral cortex. The role of NBM cholinergic projections to medial septum and then to hippocampus on spatial learning and memory, hippocamal EEG in animal model of Alzheimer's disease was assessed after unilateral lesion of NBM with phtalic acid [300 ng/kg]. Physostigmine was infused into the medial septum. Forty wistar male rats were divided in 4 groups: control, lesioned, lesioned received saline and lesioned treated with physostigmine [5microg/microl]. Animals were operated stereotaxicaly for NBM lesioning, intramedial septum cannulation and hippocamal electrode implantation. Rats were trained one session daily into T-maze and alterations of hippocampal EEG amplitude were evaluated. The results showed intramedial septum infusion of physostigmine improves spatial learning and memory in lesioned animals significantly [p<0.01]. NBM cholinergic projections to medial septum and then the hippocampus as well as its projections to amygdala and cortex have a role in spatial learning and memory. Administration of physostigmine improves decrease of hippocampal EEG amplitiude, spatial learning and memory impairment that was induced by NMB lesioning in male rats

Effects of the Panax notoginseng saponins on the level of synaptophysin protein in brain in rat model with lesion of Meynert / 中国中药杂志

<p><b>OBJECTIVE</b>To observe the protective effect of Panax notoginseng saponins (PNS) on the level of synaptophysin ptotein in brain in rat model with Alzheimer's disease (AD).</p><p><b>METHOD</b>The AD rat models were established by intra-peritoneal injection of D-galactose combined with excitatory neurotoxin ibotenic acid injection into bilateral nbM. The activity and content of synaptophysin protein in brain were determined by immunohistochemistry analysis.</p><p><b>RESULT</b>PNS could reduce the lesion of level of synaptophysin protein in brain, as compared with those of model group's rats.</p><p><b>CONCLUSION</b>PNS plays a protective role by reducing down of the level of synaptophysin protein in brain in lesion of AD animal model.</p>

Reactivation of metabolically impaired neurons in Alzheimer’s disease

Several lines of evidence show that decreased metabolic rate precedes cognitive impairment in Alzheimer ’s disease (AD). Decreased neuronal metabolism contributes to neuronal atrophy and functional impairment and is thus an early occurring hallmark of AD. Factors that may contribute to a diminishment in neuronal metabolism are age, sex, APOE-ε 4 and decreased levels of sex hormones or melatonin. Several observations in postmortem brain indicate that activated neurons are better able to withstand aging and AD, a phenomenon we paraphrased as “use it or lose it”. Moreover, a number of pharmacological and non-pharmacological studies support the concept that activation of the brain has beneficial effects and may to a certain degree restore several aspects of cognition and other central functions. For instance, the circadian system of Alzheimer patients may be restimulated by exposing them to more light or transcutaneous nerve stimulation. A procedure allowing testing of the efficacy of putative stimulatory compounds such as neurotrophins and precursor cells has been developed in order to be able to culture human postmortem brain tissue.

El espacio perforado anterior y sus zonas aledañas con consideraciones funcionales. Parte II / The anterior drilled space and its sorrounding areas with functional considerations. Part II

Los vasos que perforan el EPA provienen de la carotida, cerebral anterior y media coroidea anterior. Tienen zonas de penetracion tipicas pero parcialmente superpuestas y su distribucion obedece a razones topograficas generadas por la estructura del EPA y condicionadas filogeneticamente. Aunque no correcta, la denominacion lenticuloestriada para los ramos silvianos, ha sido impuesta por el uso. Funcionalmente, se distinguen tres sistemas no separables anatomicamente, el palido ventral, el nucleo basal y la amigdala - septum, que confieren el EPA su actividad relevante en procesos de memoria, atencion, conducta y personalidad

Effects of D-galactose combined with lesions of nucleus basalis of Meynert on hippocampal long-term potentiation and synaptic morphology / 中国应用生理学杂志

<p><b>AIM</b>To study the changes of synaptic plasticity in rat model with Alzheimer disease (AD).</p><p><b>METHODS</b>AD rat model was conducted by D-galactose intraperitoneal injection combined with lesions of nucleus basalis of Meynert (nbM). Behavioral performance, LTP in dentate gyrus and synaptic morphology in hippocampal CA1 were observed.</p><p><b>RESULTS</b>(1) Escape latencies in place test in model rats were longer than that in control rats, and swimming time and distance between the two groups in platform quadrant were significant differently (P < 0.01). (2) The numerical density (Nu) and surface density (Su) of synaptic contact zones markedly decreased (P < 0.01) in model rats. (3) Augment of population spike (PS) in perforant path-dentate gyrus of model rats after high frequency stimulation was smaller than that of the control (P < 0.05).</p><p><b>CONCLUSION</b>The results suggest that the decreased synaptic plasticity in hippocampus could responsible for the impairment of spatial learning of model rats.</p>

Pharmacological Approach to Demented Patients

Of all patients with dementia, 50-60% have dmentia of Alzheimer's type, and vascular dementia represents 17-29% of all cases. Other common causes of dementia include drugs, toxins, intracranial masses, anoxia, infections, neurodegenerative disorders, metabolic disorders, and chronic infalmmatory disorders. Treatment approach to demented patients may account for drug therapy in Al-zheimer's disease, because about 10-23% of patients have coexisting vascular dementia and dementia of Alzheimer's type. Dementia other than Alzheimer's disease also show various degrees of impairment of cognitive and non-cognitive function such as depression, psychosis and other behavioral problems, therefore pharmacological treatment for specific symptoms should be provided and therapy should be directed toward treating the underiying cuases as well. Alzheimer's disease (AD) is the most important of all the degenerative disease with progressive impairment of cognitive function and neuropsychiatric disturbance. Neuropathologic investigations have shown that cholinergic neuronal loss is seen in the nucleus basalis of Meynert, and choline acetyltransferase and acctylcholine esterase are decreased in the cerebral cortex. This hypothesis led to attempts to correct the dificiency with cholinomimetic agents and proved to be effective in some patients. However, there have been no pharmacologic agent proved to be suce-ssful. The most recent of these is the reversible acetyl cholinesterase inhibitor with long half life and high affirnity to CNS, Aricept (donepezil), which produces great improvement in cognitive function in clinical trials in Europe and US without compromized hepatotoxicity. The other pathophysiology of AD includes wide range of neurotransmitter imbalances and cortical atrophy, so that combined treatment apporach such as choinergic/serotonergic drug and cholinergic/somatostatinergic drug should be considered. As a preventive approach, neurotrophic factor, which may delay degenerative process of cholinergic neuron, is clinically valuable when administrated directly into ventricles. In many cases, amyloid deposits are seen as the distinctive neuropathology of AD, and the evidence that amyloid peptide genes found to be on chromosome 21 will lead the gene therapy for this diseases. As the disease advances, various degrees of neuropsychiatric distrubance become so marked that may be helped by treatment of associated depression, anxiety, disruptive behavior, and psychotic symtoms with appropriate psychotropic medication. However, these drugs may make patients confused, requiring reduced ro withdrawal of the medication. therefore, a careful attempt should be made, since demands on enviromental apporach and behavioral therapy are high.

Choline Acetyltransferase Immunohistochemical Studies on Basal Nucleus of Meynert and Vestibular Nucleus of Pyrithiamine-Induced Thiamine Deficient Rats

Thiamine deficiency is generally accepted as the primary etiologic factor for the Wernicke encephalopathy in human and for the similar neurologic symptoms in thiamine depleted experimental animals. Although pyrithiariiineinduced thiamine deficiency has been known to produce histopathologic lesions within many nuclei of the rat brain, the pathogenic mechanisms involved have not been clarified. Furthermore, the effect of thiamine deprivation on the nature and anatomic distribution of neurotransmitter changes has not been fully explored. The present studies were undertaken to investigate - morphological changes of the basal nucleus of Meynert and vestibular nucleus in thiamine deficient rats induced by pyrithiamine and thiamine deficient diet. For this purpose immunohistochemical stain for choline acetyltransferase was performed. Fifty healthy Sprague-Dawley strain rats weighing about 150 gm, were divided into 10 control group and 40 thiamine deficient group. Animals in thiamine deficient group were treated with daily intraperitoneal injection of pyrithiamine( 50 ug/lOOgm of BW/dbLy, Sigma Co.) for 9 days and were continuously given thiamine deficient diet until to be sacrificed. Thiamine deficient rats were subdivided into 3 groups according to different stages of neurologic manifestations ; the early group, the beginning stage of anorexia, hypothermia and weight loss without neurologic manifestations(sacrificed day ; 9th-13th day) the intermediate group, the developing stage of gait ataxia and hypotonia(sacrificed day ; 17th-19th day) the late group, the established stage of tremor, convulsion and back arching(sacrificed day ; 23th-26th day). All animals were anesthetized with sodium pentobarbital(40mg/kg, I.p.) and perfused in vivo through the ascending aorta with 10% neutral buffered formalin or 4% paraformaldehyde-0. 1% glutaraldehyde in PBS, and then brains were removed. Luxol-fast blue and cresyl violet stain was performed according to routine paraffin method for observing morphologic changes in basal nucleus of Meynert and vestibular nucleus. In addition immunohistochemical stains in the same regions were performed by free floating method in cell culture plate. All preparations were observed with a light microscope. The results obtained were as follows ; 1. Sequential changes of the neurologic manifestations in thiamine deficient rats were weight loss, hypothermia and ariorexia on the 9th-10th day, followed by gait ataxia and hypotonia on the 13th-15th day, and then tremor, convulsion and back arching on the 22th-26th day. 2. Glial proliferation was noted in the basal nucleus of the early group but not in the vestibular nucleus. Atrophy and pyknosis of neurons in basal nucleus and vestibular nucleus were shown in the intermediate group and marke neuronal loss and edematous tissue necrosis were noted in the late group. 3. Choline acetyltransferase immurforeactivity in the basal nucleus and vestibular nucleus was markedly positive in the early group as well as control group, moderately positive in the intermediate groupand minimally positive in the late group. It is suggested that the extent of neuronal damage in thiamine deficient rats is proportional to the duration of thiamine depletion. And the data presented here may account for: the regional susceptability and reversibility of certain symptoms in thiamine deficient rats.