Stereological study of the neuronal number and volume of 38 brain subdivisions of subjects diagnosed with autism reveals significant alterations restricted to the striatum, amygdala and cerebellum

Abstract

IntroductionA total of 38 brain cytoarchitectonic subdivisions, representing subcortical and cortical structures, cerebellum, and brainstem, were examined in 4- to 60-year-old subjects diagnosed with autism and control subjects (a) to detect a global pattern of developmental abnormalities and (b) to establish whether the function of developmentally modified structures matches the behavioral alterations that are diagnostic for autism. The volume of cytoarchitectonic subdivisions, neuronal numerical density, and total number of neurons per region of interest were determined in 14 subjects with autism and 14 age-matched controls by using unbiased stereological methods.ResultsThe study revealed that significant differences between the group of subjects with autism and control groups are limited to a few brain regions, including the cerebellum and some striatum and amygdala subdivisions. In the group of individuals with autism, the total number and numerical density of Purkinje cells in the cerebellum were reduced by 25% and 24%, respectively. In the amygdala, significant reduction of neuronal density was limited to the lateral nucleus (by 12%). Another sign of the topographic selectivity of developmental alterations in the brain of individuals with autism was an increase in the volumes of the caudate nucleus and nucleus accumbens by 22% and 34%, respectively, and the reduced numerical density of neurons in the nucleus accumbens and putamen by 15% and 13%, respectively.ConclusionsThe observed pattern of developmental alterations in the cerebellum, amygdala and striatum is consistent with the results of magnetic resonance imaging studies and their clinical correlations, and of some morphometric studies that indicate that detected abnormalities may contribute to the social and communication deficits, and repetitive and stereotypical behaviors observed in individuals with autism.

Autistic-Like Traits and Cerebellar Dysfunction in Purkinje Cell PTEN Knock-Out Mice

“…PC loss has been observed in several autopsy studies of autistic patients (Palmen et al, 2004;Whitney et al, 2008;Skefos et al, 2014;Wegiel et al, 2014). Regarding animal models, Lurcher chimeric mice, which show cerebellar abnormalities including postnatal loss of PCs, display behavioral inflexibility and repetitive behavior (Martin et al, 2010).…”

“…The cerebellum is involved not only in the control of balance, motor coordination, and learning, but also in higher order emotional, social, and cognitive functions, mainly through its projections (via the thalamus) to various cortical regions including the prefrontal, parietal, and limbic cortex (Fatemi et al, 2012;Reeber et al, 2013;Strick et al, 2009). Notably, Purkinje cell (PC) loss is one of the most common anatomical abnormalities seen in autopsy studies of autistic patients (Palmen et al, 2004;Whitney et al, 2008;Skefos et al, 2014;Wegiel et al, 2014). Cerebellar injury has been associated with a high incidence of ASDs (Wang et al, 2014), and patients with diseases confined to the cerebellum often demonstrate abnormalities seen in ASDs (Schmahmann, 1998).…”

Predictive role of external carotid artery vasospasm on cerebral ischemia in subarachnoid hemorrhage: experimental study

“…The affected structures are hippocampal region with the CA fields, the dentate gyrus, and the subicular complex and the adjacent perirhinal, entorhinal, and parahippocampal gyrus (45). Studies have shown psychiatric co-morbidities in temporal lobe epilepsy and temporal lobe atrophy in relation to Alzheimer's disease (13,22,36,51,66).…”

Do gap junctions regulate synchrony in the Parkinsonian basal ganglia?

“…Given a resolution of the confocal microscope of around 1 µm in axial direction, this density scales to 9 · 10 5 puncta/mm 3 . With a neuron density of 2,485 neurons/mm 3 in the human GPe [Wegiel et al, 2014], we get 362 puncta/neuron, and thus on average around 3.6 functional gap junctions per neuron. In PD patients, we detected around 1,300 puncta/mm 2 , which relates to roughly 5.2 functional gap junctions per neuron.…”

“…Given a network of 300 GPe neurons, a connection probability of 1.4 % would be equivalent to on average 2.1 unidirectional synapses per neuron. However, for realistic numbers of neurons -about 45,960 neurons in the rat GP [Oorschot, 1996] or about 904,365 neurons in the human GPe [Wegiel et al, 2014] -we would estimate a much higher number of synapses per neuron. It thus makes more sense to consider the number of inputs that a GPe neuron receives from other neurons.…”