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.

Evaluation of magnocellular pathway abnormalities in schizophrenia: a frequency doubling technology study and clinical implications / Avaliação das alterações da via magnocelular na esquizofrenia usando FDT e suas implicações clínicas

BACKGROUND: Visual processing deficits have been reported for patients with schizophrenia. Previous studies demonstrated differences in early-stage processing of schizophrenics, although the nature, extent, and localization of the disturbance are unknown. The magnocellular and parvocellular visual pathways are associated with transient and sustained channels, but their respective contributions to schizophrenia-related visual deficits remains controversial. PURPOSE: The aim of this study was to evaluate magnocellular dysfunction in schizophrenia using frequency doubling technology. METHODS: Thirty-one patients with schizophrenia and 34 healthy volunteers were examined. Frequency doubling technology testing was performed in one session, consisting of a 15-minute screening strategy followed by the C-20 program for frequency doubling technology. RESULTS: Schizophrenic patients showed lower global mean sensitivity (30,97 ± 2,25 dB) compared with controls (32,17 ± 3,08 dB), p<0.009. Although there was no difference in the delta sensitivity of hemispheres, there was a difference in sensitivity analysis of the fibers crossing the optic chiasm, with lower mean sensitivity in the patient group (28,80 dB) versus controls (30,66 dB). The difference was higher in fibers that do not cross the optic chiasm, with lower mean sensitivity in patients (27,61 dB) versus controls (30,26 dB), p<0.005. CONCLUSIONS: Our results suggest that there are differences between global sensitivity and fiber sensitivity measured by frequency doubling technology. The different sensitivity of fibers that do not cross the optic chiasm is consistent with most current etiological hypotheses for schizophrenia. The decreased sensitivity responses in the optic radiations may significantly contribute to research assessing early-stage visual processing deficits for patients with schizophrenia.

HISTÓRICO: Déficits de processamento visual foram relatados em pacientes com esquizofrenia. Estudos anteriores demonstraram diferenças no estágio inicial de processamento de esquizofrênicos, embora a natureza, extensão e localização do distúrbio são desconhecidas. As vias magnocelulares e parvocelular visuais são associados com canais transitórios e sustentado, mas suas respectivas contribuições para a esquizofrenia relacionados com déficits visuais permanece controverso. OBJETIVO: Avaliar a disfunção magnocelular na esquizofrenia usando a tecnologia de frequência dupla. MÉTODOS: Trinta e um pacientes com esquizofrenia e 34 voluntários saudáveis ​​foram examinados. Tecnologia de frequência dupla foi realizada em uma sessão, consistindo de uma estratégia de rastreio de 15 minutos, seguido do programa de C-20 para tecnologia de frequência dupla. RESULTADOS: Os pacientes esquizofrênicos apresentaram sensibilidade média inferior global (30,97 ± 2,25 dB), em comparação com os controles (32,17 ± 3,08 dB), p<0,009. Embora não tenha ocorrido diferença na sensibilidade do delta de hemisférios, houve uma diferença na análise de sensibilidade das fibras que atravessam a quiasma, com menor sensibilidade média no grupo de pacientes (28,80 dB) versus controlos (30,66 dB). A diferença foi maior em fibras que não cruzam o quiasma óptico, com menor sensibilidade média em pacientes (27,61 dB) versus controles (30,26 dB), p<0,005. CONCLUSÕES: Nossos resultados sugerem que há diferenças entre a sensibilidade global e sensibilidade da fibra medida pela tecnologia de frequência dupla. A sensibilidade diferente de fibras que não cruzam o quiasma óptico é compatível com a maioria das atuais hipóteses etiológicas para a esquizofrenia. As respostas diminuição da sensibilidade nas radiações ópticas podem contribuir significativamente para pesquisar a avaliação em estágio inicial déficits de processamento visual em pacientes com esquizofrenia.

Establishment of a Mouse Model of Alzheimer Dementia / 医学研究杂志

Objective To establish a Alzheimer dementia(AD) model in mice. Methods The C57BL/6 mice were lesioned with ibotenic acid in Nucleus basalis of Meynert(NBM). Behavioral tests by eight-arm radial maze were conducted 8 weeks, and immunohistochemical staining of choline acetyltransferase(ChAT), serotonin(5-HT), GAD(GABA), amyloid-?protein (AP) was conducted 12 weeks after NBM lesioning. Results In NBM lesioned mice, the ChAT-positive neurons, serotonin-positive neurons, and GAD-positive neurons in right NBM reduced, and ChAT-positive neurons reduced most evidently. At the same time, the ChAT-positive fibers in prefrontal and parietal cortices decreased significantly, serotonin-positive axons slightly, accompanied by heavily AP co-expression. On the contrary, there was no change of GAD-positive neurons in cortex. The working memory error increased significantly.Conclusion Ibotenic acid lesioning in NBM can provide as a model of AD in that it produces deafferentation of cholinergic system and recent memory disruption.

EFFECTS OF CORTICOTROPIN RELEASING FACTOR ON LEARNING AND MEMORY IN THE NUCLEUS BASALIS OF MEYNERT IN RATS / 神经解剖学杂志

The present study was performed to explore the role of corticotropin releasing factor (CRF) in the nucleus basalis of Meynert (NBM) in spatial learning and memory of rats. The latency, distance and swimming path to find the platform were measured by Morris water maze after intra-NBM injections of 0, 0.01, 0.1 and 0.4 nmol of CRF. Intra-NBM injections of 0.1 or 0.4 nmol of CRF induced significant increase of the latency for spatial learning and memory, and there were no significant changes in the swimming speed in Morris water maze test. The results suggest that CRF plays an inhibitory role in spatial learning and memory consolidation in the NBM of rats.

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.

Muscarine M2 Receptor-mediated Presynaptic Inhibition of GABAergic Transmission in Rat Meynert Neurons

Cholinergic modulation of GABAergic spontaneous miniature inhibitory postsynaptic currents (mIPSCs) by the activation of muscarine receptors was investigated in mechanically dissociated rat nucleus basalis of the Meynert neurons using the conventional whole-cell patch recording configuration. Muscarine (10microM) reversibly and concentration-dependently decreased mIPSC frequency without affecting the current amplitude distribution. Muscarine action on GABAergic mIPSCs was completely blocked by 1microM methoctramine, a selective M2 receptor antagonist, but not by 1microM pirenzepine, a selective M1 receptor antagonist. NEM (10microM), a G-protein uncoupler, attenuated the inhibitory action of muscarine on GABAergic mIPSC frequency. Muscarine still could decrease GABAergic mIPSC frequency even in the Ca2+-free external solution. However, the inhibitory action of muscarine on GABAergic mIPSCs was completely occluded in the presence of forskolin. The results suggest that muscarine acts presynaptically and reduces the probability of spontaneous GABA release, and that such muscarine-induced inhibitory action seems to be mediated by G-protein-coupled M2 receptors, via the reduction of cAMP production. Accordingly, M2 receptor-mediated disinhibition of nBM neurons might play one of important roles in the regulation of cholinergic outputs from nBM neurons as well as the excitability of nBM neurons themselves.

THE EXPRESSION OF TrkA AND ChAT IN THE BASAL NUCLEUS OF MEYNERT IN RATS OF DIFFERENT AGE / 神经解剖学杂志

The distribution of TrkA and the postnatal development(PD) of TrkA and ChAT-immunoreactive(-IR) neurons andthe relation between them in the basal nucleus of Meynert of rats were studied with immunohistochemical method. The number,mean profile areas and grey degree of TrkA-IR and ChAT-IR neurons were examined with image analyser. The data revealed thatTrkA-IR neurons were localized in the basal forebrain of rats. TrkA immunostaining was present at PDI, but ChAT was not.ChAT immunostaining was present at PD5. Most densely stained TrkA and ChAT neuronal bodies and fibers were present atPD20, the mean grey degrees of TrkA-IR and ChAT-IR neuronal profiles reached its peak. Both TrkA and ChAT neurons beganto cline at PD30 and maintained a relatively higher level in the adult. However, during aging both TrkA and ChAT-IR neuronsatrophy and became smaller than that in the adult. The number of TrkA-IR and ChAT-IR neurons were decreased by 41.38% and 51.61%; the mean profile areas decreased by 15.7% and 12.8%; and the mean grey degrees by 29.9% and 9.9%, respec-tively. The mean profile areas of TrkA-IR and ChAT-IR neurons from PD5 to aged rats were positively correlated. The resultsindicated that the expression of TrkA was earlier than ChAT. The expression of TrkA and ChAT followed a very similar tempo-ral pattern in the basal nucleus of Meynert from PD5 to aged rats, suggesting that TrkA might participate the regulation ofChAT-IR neuronal development, differentiation, maturation, and ageing. The down-regulation of TrkA and ChAT of aged ratsis associated with neuronal atrophy and loss and may contribute to the pronounced vulnerability of these neurons to degenerationin aging animals and Alzheimer's disease.

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.

EFFECTS OF GINSENOSIDES ON BDNF IN NUCLEUS BASALIS OF MEYNERT AND CEREBRAL CORTEX OF AGED RATS / 解剖学报

Objective To observe the age-related changes of brain-derived neurotrophic factor(BDNF) and investigate the effects of ginsenosides(GS) on BDNF in nucleus basalis of Meynert(NBM) and cerebral cortex of aged rats. Methods Twenty-four female Wistar rats were randomly divided into 3 groups: young group(3-5 months),aged groups(27 months) and GS group(27 months).GS group was fed with GS from 18 to 27 months.Immunohistochemistry and Imaging analysis were used to show the expression and distribution of BDNF in NBM and cerebral cortex of each group. Results BDNF level of aged group was much lower than that of young group in these two brain areas(P