Biology subjects

Sesia, T.

Publications and source records attributed to Sesia, T..

3 recordsLinked to original sources

bioRxiv2023

TgF344-AD rat model of Alzheimer's disease: spatial disorientation and asymmetry in hemispheric neurodegeneration

BACKGROUNDThe TgF344-AD ratline represents a transgenic animal model of Alzheimers disease (AD). We previously reported spatial memory impairment in TgF344-AD rats, yet the underlying mechanism remained unknown. We, therefore, set out to determine if spatial memory impairment in TgF344-AD rats is attributed to spatial disorientation. Also, we aimed to investigate whether TgF344-AD rats exhibit signs of asymmetry in hemispheric neurodegeneration, similar to what is reported in spatially disoriented AD patients. Finally, we sought to examine how spatial disorientation correlates with working memory performance. METHODSTgF344-AD rats were divided into two groups balanced by sex and genotype. The first group underwent the delayed match-to-sample (DMS) task for the assessment of spatial orientation and working memory, while the second group underwent positron emission tomography (PET) for the assessment of glucose metabolism and microglial activity as in-vivo markers of neurodegeneration. Rats were 13 months old during DMS training and 14-16 months old during DMS testing and PET. RESULTSIn the DMS task, TgF344-AD rats were more likely than their wild-type littermates to display strong preference for one of the two levers, preventing working memory testing. Rats without lever-preference showed similar working memory, regardless of their genotype. PET revealed hemispherically asymmetric clusters of increased microglial activity and altered glucose metabolism in TgF344-AD rats. CONCLUSIONSTgF344-AD rats display spatial disorientation and hemispherically asymmetrical neurodegeneration, suggesting a potential causal relationship consistent with clinical observations. In rats without spatial disorientation, working memory remains intact.

neuroscience↗

bioRxiv2023

Phonic Tics in a Rat Model of Tourette Syndrome Enable Research on Symptom-Based DBS

The lack of a rodent model for both motor and phonic tics hinders research on deep brain stimulation (DBS) for refractory Tourette syndrome (TS). Striatal disinhibition with a GABA-A antagonist (bicuculline) was previously shown to induce tic-like hyperkinesia in rats and monkeys, while tic-like vocalizations were studied and confirmed only in the latter. We, therefore, assessed whether vocalizations accompany hyperkinesia also in rats and whether they respond to thalamic DBS. Rats underwent surgical implantation of a unilateral guide cannula targeting the caudate putamen (CPu) or nucleus accumbens (NAc). Additionally, they were implanted with an ipsilateral stimulation electrode targeting the border between the central medial (CM) and ventrolateral (VL) thalamic nuclei. Motor changes and ultrasound vocalizations were recorded and characterized offline. Bicuculline in CPu led to the development of hyperkinesia in the form of arrhythmic, myocloniform shoulder jerks sporadically alternating with episodes of dystonic lordosis. Likewise, bicuculline in NAc resulted in hyperkinesia, but at a much smaller dose and in conjunction with nonsensical vocalizations. DBS of CM/VL, but not adjacent regions, attenuated hyperkinesia. Also, early results indicate that thalamic DBS attenuates vocalizations, yet the hotspot for stimulation remains to be determined. In conclusion, striatal disinhibition leads not only to the development of hyperkinesia but also vocalizations in rats. The resemblance of hyperkinesia to motor tics and vocalizations to phonic tics is evident in their appearance and susceptibility to DBS. Rats can, therefore, be used to study DBS for symptom-based TS therapy.

animal behavior and cognition↗

bioRxiv2019

Cognitive Improvements after Intermittent Deep Brain Stimulation of the Nucleus Basalis of Meynert in a Transgenic Rat Model for Alzheimer’s disease; a Preliminary Approach

BackgroundDeep brain stimulation (DBS) of the nucleus basalis of Meynert (NBM) has shown to have promising results in a pilot study with patients suffering from Alzheimers disease (AD). A recent study in aged monkeys shows a novel intermittent stimulation pattern to have superior cognitive benefits over continuous paradigms.\n\nObjective/HypothesisWe aimed at comparing the cognitive effects elicited by intermittent and continuous NBM stimulation paradigms in an animal model for AD (TgF344-AD rat line; TG), i.e. rats expressing mutant human amyloid precursor protein (APPsw) and presenilin 1 (PS1{Delta}E9) genes, each independent causes of early-onset familial AD.\n\nMethodsIn this exploratory study, aged APP/PS1 rats were tested pre-, and post implantation with several stimulation parameters, i.e. unilateral- or bilateral-intermittent, and bilateral-continuous, while performing various behavioral tasks (open field, novel object recognition, and modified Barnes maze).\n\nResults and ConclusionBilateral-intermittent NBM DBS allowed aged TG rats to perform better and maintain their performance longer in a spatial memory task, as compared to other conditions. These data support the notion that NBM DBS could be further refined in the clinic, thereby improving patient care.

neuroscience↗