Immunohistochemical estimation of brain choline acetyltransferase and somatostatin related to the impairment of avoidance learning induced by thiamine deficiency

Nakagawasai, Osamu; Tadano, Takeshi; Hozumi, Soichi; Tan-No, Koichi; Niijima, Fukie; Kisara, Kensuke

doi:10.1016/s0361-9230(00)00248-3

Cited by 35 publications

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“…Modifying a task such that reward expectancies can be used to solve the task requires the amygdala [5,48]. Second, the intensity of ChAT positive fibers in the amygdala remains unchanged after thiamine deficiency in mice [36]. Our ChAT immunocytochemistry data provide evidence that the loss (hippocampus) or sparing (amygdala) of ChAT-positive fibers reported in the Nakagawasai paper is due to a decrease of cells staining positive for ChAT in the MS/DB, but not the NBM.…”

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confidence: 51%

Section: Nih Public Accessmentioning

confidence: 99%

“…Furthermore, these authors found that acetylcholinesterase (AChE) activity was decreased in both the hippocampus and cortex after PTD treatment [42]. In addition, compounds that enhance ACh levels decrease mortality and sickness behaviors (attacking, antinociception, altered startle response) as well as improve learning in thiaminedeficient mice [36] and spontaneous alternation in PTD-treated rats [unpublished data].Reviews of the pathology produced by the PTD treatment have consistently demonstrated that although mild to moderate cell loss occurs outside the diencephalon, the anterior and midline thalamic damage are critical and responsible for the majority of the loss of learning and memory function that occurs after thiamine deficiency [26,29]. These changes, along with the white matter loss that occurs in key fiber tracts from the diencephalon after PTD treatment [27], suggest that thiamine deficiency likely causes system level dysfunction.…”

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confidence: 99%

“…We have previously documented a loss of choline acetyltransferase (ChAT) immunopositive neurons in the medial septal/diagonal band (MS/ DB) in the PTD model using a profile counting method [43,44]. Furthermore, Nakagawasai and colleagues [36,37,38] have demonstrated a decrease in the intensity of ChAT positive fibers in the hippocampus, cortex and thalamus after thiamine deficiency. However, this decrease in ChAT immunoflorescence is not observed in the amygdala.…”

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Selective septohippocampal – but not forebrain amygdalar – cholinergic dysfunction in diencephalic amnesia

2007

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A rodent model of diencephalic amnesia, pyrithiamine-induced thiamine deficiency (PTD), was used to investigate diencephalic-limbic interactions. In-vivo acetylcholine (ACh) efflux, a marker of memory-related activation, was measured in the hippocampus and the amygdala of PTD-treated and pair-fed (PF) control rats while they were tested on a spontaneous alternation task. During behavioral testing, all animals displayed increases in ACh efflux in both the hippocampus and amygdala. However, during spontaneous alternation testing ACh efflux in the hippocampus and the alternation scores were higher in PF rats relative to PTD-treated rats. In contrast, ACh efflux in the amygdala was not suppressed in PTD treated rats, relative to PF rats, prior to or during behavioral testing. In addition, unbiased stereological estimates of the number of choline acetyltransferase (ChAT) immunopositive neurons in the medial septal/diagonal band (MS/DB) and nucleus basalis of Meynert (NBM) also reveal a selective cholinergic dysfunction: In PTD-treated rats a significant loss of ChAT-immunopositive cells was found only in the MS/DB, but not in the NBM. Significantly, these results demonstrate that thiamine deficiency causes selective cholinergic dysfunction in the septohippocampal pathway. Keywords diencephalon; hippocampus; amygdala; microdialysis; acetylcholine; stereology Selective septohippocampal-but not forebrain amygdalarcholinergic dysfunction in diencephalic amnesiaDiencephalic lesions are seen in a range of disorders: malnourishment, ischemic infarcts, viral infections, tumors and traumatic damage. Damage to certain nuclei and fiber systems within the diencephalon interrupts the flow of information between key memory structures and thus causes severe and long-lasting amnesia [25,29,45]. Although there is evidence that lesions to particular diencephalic nuclei result in memory impairment in their own right, there is also evidence that damage to diencephalic nuclei can disrupt memory circuits leading to dysfunction in other regions of the brain [4,29,45,49,53].Corresponding author: Lisa M. Savage, Department of Psychology, Binghamton University, State University of New York, Binghamton, NY, 13902, e-mail: lsavage@binghamton.edu, fax: 607-777-4890. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. At one point, WKS patients were labeled as "temporal lobe-related amnesiacs" based on their memory performance [10]. This clinical population was critical for the development of the memory system classifications (i.e., declarative vs. nondeclarative memory [51]). However, it is clear from...

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confidence: 51%

Section: Nih Public Accessmentioning

confidence: 99%

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confidence: 99%

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Selective septohippocampal – but not forebrain amygdalar – cholinergic dysfunction in diencephalic amnesia

2007

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“…Rats exposed to TD show a 30% loss of choline acetyltransferase (ChAT) positive neurons in the basal forebrain (Pitkin & Savage, 2001,2004 and reduced fluorescence intensity of ChAT Wbers in the cortex, hippocampus, and thalamus (Nakagawasai et al, 2000). In addition, in PTD-treated rats there is also reduced hippocampal ACh efflux during spontaneous alternation (Savage et al, 2003).…”

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Blunted hippocampal, but not striatal, acetylcholine efflux parallels learning impairment in diencephalic-lesioned rats

Roland

Savage

2007

Neurobiology of Learning and Memory

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A rodent model of diencephalic amnesia, pyrithiamine-induced thiamine deficiency (PTD), was used to investigate the dynamic role of hippocampal and striatal acetylcholine (ACh) efflux across acquisition of a nonmatching-to-position (NMTP) T-maze task. Changes in ACh efflux were measured in rats at different time points in the acquisition curve of the task (early= day 1, middle = day 5, and late = day 10). Overall, the control group had higher accuracy scores than the PTD group in the latter sessions of NMTP training. During the three microdialysis sampling points, all animals displayed significant increases in ACh efflux in both hippocampus and striatum, while performing the task. However, on day 10, the PTD group showed a significant behavioral impairment that paralleled their blunted hippocampal-but not striatal-ACh efflux during maze training. The results support selective diencephalic-hippocampal dysfunction in the PTD model. This diencephalichippocampal interaction appears to be critical for successful episodic and spatial learning/memory.

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Supplemental thiamine as a practical, potential way to prevent Alzheimer's disease from commencing

Fessel

2021

A&D Transl Res & Clin Interv

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It is better to attempt stopping Alzheimer's disease (AD) before it starts than trying to cure it after it has developed. A cerebral scan showing deposition of either amyloid or tau identifies those elderly persons whose cognition is currently normal but who are at risk of subsequent cognitive loss that may develop into AD. Synaptic hypometabolism is usually present in such at‐risk persons. Although inadequate adenosine triphosphate (ATP) may cause synaptic hypometabolism, that may not be the entire cause because, in fact, measurements in some of the at‐risk persons have shown normal ATP levels. Thiamine deficiency is often seen in elderly, ambulatory persons in whom thiamine levels correlate with Mini‐Mental State Examination scores. Thiamine deficiency has many consequences including hypometabolism, mitochondrial depression, oxidative stress, lactic acidosis and cerebral acidosis, amyloid deposition, tau deposition, synaptic dysfunction and abnormal neuro‐transmission, astrocyte function, and blood brain barrier integrity, all of which are features of AD. Although the clinical benefits of administering supplementary thiamine to patients with AD or mild cognitive impairment have been mixed, it is more likely to succeed at preventing the onset of cognitive loss if administered at an earlier time, when the number of aberrant biochemical pathways is far fewer. Providing a thiamine supplement to elderly persons who still have normal cognition but who have deposition of either amyloid or tau, may prevent subsequent cognitive loss and eventual dementia. A clinical trial is needed to validate that possibility.

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Immunohistochemical estimation of brain choline acetyltransferase and somatostatin related to the impairment of avoidance learning induced by thiamine deficiency

Cited by 35 publications

References 36 publications

Selective septohippocampal – but not forebrain amygdalar – cholinergic dysfunction in diencephalic amnesia

Selective septohippocampal – but not forebrain amygdalar – cholinergic dysfunction in diencephalic amnesia

Blunted hippocampal, but not striatal, acetylcholine efflux parallels learning impairment in diencephalic-lesioned rats

Supplemental thiamine as a practical, potential way to prevent Alzheimer's disease from commencing

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