The septo-hippocampal neurons (SHNs), located in the medial septum, project to the hippocampal formation. The population of SHNs, as shown by single unit recordings in urethane-anesthetized rats, is heterogeneous, both in terms of patterns of spontaneous activity (a significant proportion of the SHNs display a characteristic rhythmically bursting activity at about 4 Hz) and of conduction velocity. Their average rate of spontaneous discharge is quite high (20 impulses per second). They are excited by the iontophoretic application of acetylcholine and various cholinergic agonists. They are also excited by some peptides such as substance P and TRH. Parallel studies in aged animals show that the physiological properties of the SHNs are altered, while their pharmacological properties seem to be unchanged. Immunohistochemical investigations using antibodies against various peptides and a monoclonal antibody against choline acetyltransferase (ChAT) show that SHNs retrogradely-labeled from the hippocampus often contain ChAT, less frequently galanin-like immunoreactivity and in a few cases enkephalin, luteinizing hormone-releasing hormone, or calcitonin gene-related peptide. In contrast, cholecystokinin, vasoactive intestinal peptide, substance P, somatostatin, dynorphin-B and neurotensin, although present in some medial septal neurons, were never observed in neurons projecting to the hippocampus.

Acetylcholine↗

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Septo-hippocampal neurons in the aged rat: relation between their electrophysiological and pharmacological properties and behavioral performances.

The performances of aged (24-26 months) rats in two behavioral tasks (passive avoidance and spontaneous alternation) have been studied. Subpopulations of old animals were found to be impaired in these tasks. Most of the impaired animals, however, were not impaired in both tasks. The properties of the septo-hippocampal neurons (SHNs) were subsequently studied in the same group of experimental animals, anesthetized with urethane, using electrophysiological techniques. The spontaneous activity of SHNs displaying a rhythmically bursting activity (RBA) was significantly higher in animals impaired in the spontaneous alternation task. The proportion of SHNs with RBA was significantly lower and the frequency of the RBA was higher in animals impaired in the passive avoidance task. The pharmacological properties of the SHNs were not significantly different in the various groups. The significance of these complex correlations with regard to the age-related alterations of SHNs properties is discussed.

Acetylcholine↗

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Age-related changes in dopaminergic and serotonergic indices in the rat forebrain.

Age-related changes in the content of dopamine (DA), homovanillic acid (HVA), dihydroxyphenylacetic acid (DOPAC), 3-methoxytyramine (3-MT), serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) in anterior cerebral cortex, hippocampus and striatum of the rat have been investigated using HPLC with electrochemical detection. A significant decrease in HVA was observed in the striatum and hippocampus of the aged (27 months) animals, as compared to the controls (2.4 to 2.6 months). A significant decrease in DA levels was also observed in the hippocampus but not in the striatum. In contrast, the level of DA in the cerebral cortex was markedly increased in the aged animals. A concomitant increase in 3-MT level was observed. Finally the level of 5-HIAA was significantly increased in striatum and hippocampus.

3,4-Dihydroxyphenylacetic Acid↗

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Age-related alterations in the properties of hippocampal pyramidal neurons among rat strains.

We compared age-related alterations in the electrophysiological and pharmacological properties of CA1 hippocampal pyramidal neurons in three strains of rats (Sprague-Dawley, Fisher 344, and Wistar) at 3-4 and 25-32 months of age, using the in vitro slice preparation. The most consistent age-related alterations in the properties of rat hippocampal neurons were: a decrease in membrane excitability, a decrease in the amplitude and duration of inhibitory postsynaptic potentials and a decreased sensitivity to the effect of the cholinergic agonist carbachol. In contrast, no consistent alterations in calcium-dependent events were observed in these strains of rats. The age-related changes in the duration of the afterhyperpolarizations (AHPs) were different (and even opposite) depending on the strain studied. Our results show that age-related changes observed in a given strain are not necessarily present in all strains of the same species.

Aging↗

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Age-related changes in parvalbumin- and GABA-immunoreactive cells in the rat septum.

The calcium binding protein parvalbumin is present in GABAergic neurons of the medial septum-diagonal band of Broca (MS-DBB) region that project to the hippocampal formation. We examined the distribution pattern, the number, and the morphological features of the parvalbumin-containing cells (parv+) in the MS-DBB region of 2- to 3-, 8- to 9-, 15- to 16-, and 26- to 27-month-old Sprague-Dawley rats. A significant reduction in the number of parv+ cells was observed as a function of age. The mean somal area of the parv+ cells was significantly reduced in the 26- to 27-month-old rats. A significant reduction in the number of parv+ cells was also observed in the 26- to 27-month-old rats in the cingulate cortex, but not in the striatum or the hippocampal formation. No significant age-related changes were observed in the number of the GABA-immunoreactive cells in the MS-DBB region nor in the cingulate cortex. In conclusion, there is an age-related decrease in the number of parv+ cells, with no change in the number of GABA-immunoreactive cells in the MS-DBB region of the rat. Because GABA and parvalbumin are colocalized in the MS-DBB neurons, the results suggest that the level of parvalbumin is decreased, but that the cells are not lost.

Aging↗

PubMedDate not supplied

NMDA receptor activation in the aged rat: electrophysiological investigations in the CA1 area of the hippocampal slice ex vivo.

The effects of aging on activation of N-methyl-D-aspartate (NMDA) receptors were studied in the CA1 field of hippocampal slices from young (2-4 months old) and aged (25-32 months old) Sprague-Dawley rats with the use of ex vivo extra- and intracellular electrophysiological recording techniques. No significant age-related changes of the unitary NMDA-receptor mediated excitatory postsynaptic potentials (EPSPs), recorded from the pyramidal cells after stimulation of the stratum radiatum in a magnesium-free medium and isolated in the presence of the non-NMDA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione, were found. Simultaneously, the magnitude of synaptic plasticity which involved NMDA receptor activation was not altered. No significant age-related modifications in the mechanisms controlling glutamate release and of postsynaptic NMDA receptor responsiveness were revealed. Considering the 30-40% decrease in NMDA binding sites in the aged hippocampus, our results suggest the occurrence of compensatory mechanisms which are discussed.

Aging↗

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[Physiopathology of dementia of the Alzheimer type: role of the amyloid beta-protein].

Biological research on Alzheimer's disease is expanding quickly, and the mechanisms of the disease are better understood today. Progress has been specially impressive in the knowledge of the brain lesions (senile plaques, neurofibrillary degeneration). It is likely that the beta-amyloid protein, which accumulates in the senile plaques plays a major role in the development of the brain lesions and, subsequently of the clinical symptoms. The metabolism of the precursor of this protein might be abnormal, leading to the beta-amyloid protein deposits. Some discrete genetic abnormalities (such as punctate mutations on the beta amyloid precursor gene) have been described recently in familial cases of the disease. It seems unlikely that such punctate mutations would be responsible for the majority of the cases. Therefore it is possible that Alzheimer's disease has multiple causes, the genetic factors being only one of them.

Aged↗

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[Neuropathologic validation of clinical diagnosis of senile dementia of the Alzheimer type].

The purpose of this work was to establish a neuropathological confirmation of the clinical diagnosis of senile dementia of the Alzheimer type (SDAT) in a group of patients prospectively studied in a geriatric hospital since 1984 (Charles Richet Study). The sample consisted of 45 cases, 35 of which had received a clinical diagnosis of SDAT and 10 others a diagnosis of either vascular or mixed dementia. The mean age at death was 85 +/- 6.9 years (range 64-97). The neuropathological diagnosis was established independently of the clinical findings. Senile lesions typical of SDAT were found in 32/35 cases, giving a 91.4% rate of clinico-pathologic agreement. However, vascular lesions were present in 10 cases (28.5%) and the final pathologic diagnosis was mixed dementia, lowering the score of agreement for SDAT to 63%. Considering that the pathological criteria for the diagnosis of SDAT are not uniform, we independently applied 3 inclusion (senile lesions) and 3 exclusion (vascular lesions) criteria for the diagnosis of SDAT to each of the 45 cases. This permitted a comparison of nine combinations of neuropathological criteria with the clinical diagnosis. The sensitivity values ranged from 37 to 80% and the specificity values ranged from 55 to 100%. The highest agreement rate with the clinical diagnosis was achieved when were associated the criterion which specified that plaques and tangles must be present in the hippocampus regardless of neocortical findings and the criterion which excluded cases with vascular lesions of any site if their volume was 50 ml or more.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

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[Standardized neurologic study in senile dementia of Alzheimer's type].

Seventy five patients affected by senile dementia of the Alzheimer type (mean age 82) have been submitted to a standardized neurological examination of 88 items. Gait abnormalities were present in 57% of the cases. Extrapyramidal symptoms (akinesia or rigidity or tremor) were noticed in 64% of the cases but they were rarely associated with a typical parkinsonian syndrome. Myoclonus was observed in only 4 patients. The gait abnormalities were significantly associated with the presence of rigidity and grasp reflex but not with other primitive reflexes. The only symptoms to be correlated with dementia severity as assessed by the Mini Mental State were rigidity and optokinetic nystagmus abolition. Tremor and amyotrophy of the hands appeared to be negatively correlated to dementia severity.

Aged↗

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[Quantified neuropsychological study in senile dementia of Alzheimer's type].

Forty six patients affected by senile dementia of the Alzheimer type and 20 control subjects of similar age, sex and educational level have been studied, using a quantified neuropsychological battery (Wechsler memory scale, Raven progressive matrices and quantified tests for aphasia, apraxia and agnosia). There was a significant correlation between the scores of all cognitive functions with one another and with the Mini Mental State. The results show a rather global impairment of cognitive functions in these patients and suggest that intellectual impairment progresses as a continuum in senile dementia of the Alzheimer type.

Aged↗

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The Hoffmann reflex (H-reflex) in senile dementia of the Alzheimer's type--preliminary results.

The Hoffmann reflex (H-reflex) and direct motor response (M) were investigated (latency, amplitude and excitability curves were analyzed) in patients with senile dementia of the Alzheimer's type (SDAT). M responses had similar latencies in SDAT patients and old control subjects. H reflex latencies were similar in SDAT patients and old control subjects but longer than in younger controls. The H max/M max ratio was also lower in SDAT patients and old control subjects than in younger controls. The excitability curve of the H-reflex (using a double shock procedure) in SDAT patients was lower than in non-demented old controls for all values of the interstimulus intervals.

Aged↗

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[Study methods of drugs in Alzheimer disease].

The availability of new drugs for Alzheimer's disease, with different pharmacological profiles, leads to a redefinition the relevant methodology for developing drugs in this indication, including the inclusion/exclusion criteria, the duration of the studies, and therefore, the relevant guidelines. This was the purpose of the Giens Round-table devoted to the new methodology for drug development in Alzheimer disease.

Alzheimer Disease↗