Combined administration of cerebrolysin and donepezil induces plastic changes in prefrontal cortex in aged mice

Cai

Experimental and Therapeutic Medicine

et al. 2014

Adult-onset hypothyroidism induces various impairments in hippocampus-dependent cognitive function, in which numerous synaptic proteins and neurotransmitters are involved. Donepezil (DON), an acetylcholinesterase inhibitor, has been shown to be efficient in improving cognitive function. The aim of the present study was to investigate the effects of adult-onset hypothyroidism on the expression levels of the synaptic proteins syntaxin-1 and munc-18, as well as the content of the neurotransmitter acetylcholine (ACh) in the hippocampus. In addition, the study explored the effects of thyroxin (T4) and DON treatment on the altered parameters. The study involved 55 Sprague-Dawley rats that were randomly divided into five groups: Control, hypothyroid (0.05% 6-n-propyl-2-thiouracil; added to the drinking water), hypothyroid treated with T4 (6 μg/100 g body weight once daily; intraperitoneal injection), hypothyroid treated with DON (0.005%; added to the drinking water) and hypothyroid treated with a combination of the two drugs (6 μg/100 g T4 and 0.005% DON). The concentration of ACh was determined in the homogenized hippocampus of each animal by alkaline hydroxylamine colorimetry. The protein levels of syntaxin-1 and munc-18 were determined by immunohistochemistry. The results showed that the content of ACh in the hippocampi of the hypothyroid rats was significantly decreased compared with that in the controls and that T4 monotherapy and DON administration restored the ACh content to normal values. In the hippocampi of the hypothyroid group, munc-18 was expressed at significantly lower levels, while the expression levels of syntaxin-1 were increased compared with the levels in the control group. Treatment with T4 alone restored the expression of syntaxin-1 but failed to normalize munc-18 expression levels. The co-administration of T4 and DON returned the munc-18 levels to normal values. These observations indicate that adult-onset hypothyroidism induces alterations in the levels of munc-18, syntaxin-1 and ACh in the hippocampus. Syntaxin-1 and ACh levels were restored by T4 monotherapy while munc-18 levels were not. In addition, the co-administration of T4 and DON resulted in more effective restoration than either alone. The thyroid hormone has a direct effect on metabolism of hippocampal ACh in adult rats and DON is helpful for treatment of synaptic protein impairment induced by hypothyroidism.

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Effects of thyroxin and donepezil on hippocampal acetylcholine content and syntaxin-1 and munc-18 expression in adult rats with hypothyroidism

Cai

Experimental and Therapeutic Medicine

et al. 2014

“…These results may suggest that dendritic spine atrophy could be interpreted as maladaptive plasticity. Several reports have demonstrated that aging‐induced dendritic length hypotrophy and spine loss are accompanied by cognitive deficits in tasks mediated by the hippocampus and the PFC (Acosta‐Peña et al, ; Alcantara‐Gonzalez et al, ; Duan et al, ; Juarez et al, ; Romero‐Curiel et al, ). In addition, reduced spinogenesis in the PFC‐, hippocampus‐pyramidal and NAcc‐medium spiny neurons has been reported in animal models of VD (Sanchez et al, ; Vega et al, ).…”

Section: Relevance Of Neuronal Morphology In Vascular Dementiamentioning

confidence: 99%

Neuronal changes after chronic high blood pressure in animal models and its implication for vascular dementia

Flores

Flores-Gómez²,

Gómez-Villalobos

2016

Synapse

Self Cite

Vascular dementia is a devastating disorder not only for the patient, but also for the family because this neurocognitive disorder breaks the patient's independence, and leads to family care of the patient with a high cost for the family. This complex disorder alters memory, learning, judgment, emotional control and social behavior and affects 4% of the elderly world population. The high blood pressure or arterial hypertension is a major risk factor for cerebrovascular disease, which in most cases leads to vascular dementia. Interestingly, this neurocognitive disorder starts after long lasting hypertension, which is associated with reduced cerebral blood flow or hypoperfusion, and complete or incomplete ischemia with cortical thickness. Animal models have been generated to elucidate the pathophysiology of this disorder. It is known that dendritic complexity determines the receptive synaptic contacts, and the loss of dendritic spine and arbor stability are strongly associated with dementia in humans. This review evaluates relevant data of human and animal models that have investigated the link between long-lasting arterial hypertension and neural morphological changes in the context of vascular dementia. We examined the effect of chronic arterial hypertension and aged in vascular dementia. Neural dendritic morphology in the prefrontal cortex and the dorsal hippocampus and nucleus accumbens after chronic hypertension was diskussed in the animal models of hypertension. Chronic hypertension reduced the dendritic length and spine density in aged rats.

Journal of Neuroscience Methods

“…The Sholl analysis was originally described by Donald Arthur Sholl in 1953 in his publication describing dendritic organization in the neurons of cat cortices (Sholl, 1953). This program computes the number of intersections in concentric annuli as a function of increasing distance from the neuron soma and has been used for decades to study dendrite development and morphology under various conditions (Aizawa et al, 2004; Alcantara-Gonzalez et al, 2012; Chen et al, 2005; Chiang et al, 2011; Milosevic and Ristanovic, 2007; Ristanovic et al, 2006; Schoenen, 1982; Sholl, 1953; Torres-Garcia et al, 2012). Finally, neuroscientists and biomedical engineers have occasionally borrowed from fiber orientation analysis to apply Fast Fourier Transform (FFT) to analyze neurite alignment (Ayres et al, 2006; Ayres et al, 2008; Levitt et al, 2007; Sander and Barocas, 2009; Sivaguru et al, 2010; Voyiadjis et al, 2011).…”

Section: 5 Discussionmentioning

confidence: 99%

Semi-automatic quantification of neurite fasciculation in high-density neurite images by the neurite directional distribution analysis (NDDA)

Hopkins

Wheeler

Staii

et al. 2014

Background Bundling of neurite extensions occur during nerve development and regeneration. Understanding the factors that drive neurite bundling is important for designing biomaterials for nerve regeneration toward the innervation target and preventing nociceptive collateral sprouting. High-density neuron cultures including dorsal root ganglia explants are employed for in vitro screening of biomaterials designed to control directional outgrowth. Although some semiautomated image processing methods exist for quantification of neurite outgrowth, methods to quantify axonal fasciculation in terms of direction of neurite outgrowth are lacking. New Method This work presents a semi-automated program to analyze micrographs of high-density neurites; the program aims to quantify axonal fasciculation by determining the orientational distribution function of the tangent vectors of the neurites and calculating its Fourier series coefficients (‘c’ values). Results We found that neurite directional distribution analysis (NDDA) of fasciculated neurites yielded ‘c’ values of ≥ ~0.25 whereas branched outgrowth led to statistically significant lesser values of <~0.2. The ‘c’ values correlated directly to the width of neurite bundles and indirectly to the number of branching points. Comparison with Existing Methods Information about the directional distribution of outgrowth is lost in simple counting methods or achieved laboriously through manual analysis. The NDDA supplements previous quantitative analyses of axonal bundling using a vector-based approach that captures new information about the directionality of outgrowth. Conclusion The NDDA is a valuable addition to open source image processing tools available to biomedical researchers offering a robust, precise approach to quantification of imaged features important in tissue development, disease, and repair.