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Aydin, A. G.

Publications and source records attributed to Aydin, A. G..

3 recordsLinked to original sources

Sound-evoked auditory neurophysiological signals are a window into prodromal functional differences in a preclinical model of Alzheimer's Disease

Hearing is the largest modifiable mid-life risk factor for Alzheimers Disease (AD), yet its link to dementia remains unclear. We identified a neurophysiological biomarker of AD risk using the non-invasive, rapidly acquired, and clinically translatable auditory brainstem response (ABR) in normal hearing knock-in rats (Swedish familial AD risk variant to Amyloid precursor protein, AppS; male and female). Human ABRs have been proposed as a biomarker for AD and related dementias. The novel metric reported here is derived from multidimensional parametric feature extraction on the distribution statistics of repeated single-trial ABR traces. We report accurate prediction of genetic risk for AD risk in young and aged rats: AppS separate clearly from healthy humanized (AppH) in sex- and age-dependent manners. Notably, auditory learning during young adulthood shifted the AppS ABR signature towards a healthy AppH-like state that maintained over time into older age. Altogether the findings support the utility of the ABR to track disease state, progression, and effects of intervention, and point to a central neural generator of auditory dysfunction related to AD risk. ABRs could provide a very early biomarker for detection of AD risk and used to test the synergy of auditory and cognitive functions in human dementia.

neuroscience↗

Functional diversities within neurons and astrocytes in the adult rat auditory cortex revealed by single-nucleus RNA sequencing.

The mammalian cerebral cortex is composed of a rich diversity of cell types. Cortical cells are organized into networks that rely on their functional diversity to ultimately carry out a variety of sophisticated cognitive functions. To investigate the breadth of transcriptional diverse cell types in the sensory cortex, we have used single-nucleus RNA sequencing (snRNA-seq) in the auditory cortex of the adult rat. A variety of unique excitatory and inhibitory neuron types were identified. In addition, we report for the first time a diversity of astrocytes in the auditory cortex that may represent functionally unique subtypes. Together, these results pave the way for building models of how neurons in the sensory cortex work in concert with astrocytes at synapses to fulfill high-cognitive functions like learning and memory.

neuroscience↗

Behavioral and Neuroanatomical Investigation of Attention Deficit Hyperactivity Disorder Pathogenesis in Juvenile Spontaneously Hypertensive Rats

Attention-deficit/hyperactivity disorder (ADHD) is one of the most prevalent neuropsychiatric disorders of childhood, characterized by locomotor hyperactivity, impaired sustained attention, impulsivity, and distractibility. Recently, the dysfunction of different synaptic circuits in the prefrontal cortex (PFC) has been shown. Previous studies have attributed the pathophysiological mechanism of ADHD to disturbances in the dopaminergic system. In this study, we tested the hypothesis that spontaneously hypertensive rats (SHR), which are considered a validated animal model of ADHD, have altered dopaminergic innervation and increased locomotor activity. Here, we performed immunohistochemical tyrosine hydroxylase (TH) and dopamine-beta-hydroxylase (DBH) staining. The mesocortical dopaminergic system appears to be normal in juvenile SHR, as suggested by (i) no alteration in the area density of TH-immunoreactive (TH-ir) dopaminergic neurons in the VTA, (ii) no alterations in the volume density of TH-ir fibers in layer I of the PrL subregion of mPFC, (iii) no alteration in the percentage of TH-ir dopaminergic fibers in layer I of the PrL subregion of mPFC as revealed by TH and/or DBH immunoreactivity. Furthermore, the SHR showed increased locomotor activity than WKY in the open field test. The demonstration of no alteration in mesocortical dopaminergic neurons and fiber in SHR raises some concern about the position of SHR as an animal model of the inattentive subtype of ADHD. However, these results strengthen this strain as an animal model of hyperactive/impulsive subtype ADHD for future studies that may elucidate the underlying mechanism mediating hyperactivity and test various treatment strategies.

neuroscience↗