Monoamine oxidase‐A and B activities in the cerebellum and frontal cortex of children and young adults with autism

Gu, Feng; Chauhan, Ved; Chauhan, Abha

doi:10.1002/jnr.24027

Cited by 24 publications

(19 citation statements)

References 49 publications

(76 reference statements)

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“…We measured serotonin turnover (5HIAA/5HT) and found a significant reduction in cortex from males exposed to PNS when compared with non-stressed controls. In addition, we found a reduction in MAO-A, an enzyme responsible for the breakdown of amines including 5HT, in the cortex of male mice exposed to PNS when compared to non-stressed controls, mirroring what was found in post-mortem tissue of children with ASD who have abnormal social behavior [31]. Together, these data reflect an overall increase in 5HT in the cortex of the male mice exposed to PNS.…”

Section: Discussionsupporting

confidence: 79%

“…In addition, we found that this early life exposure affects cortical 5HT metabolism, elevated markers of neuroinflammation, and oxytocin, as well as corticosterone levels in response to social interaction. This constellation of changes reflects neurobiological changes seen in individuals with ASD [9,31,42,43,50–52]. Our findings suggest that the roots of the psychopathology of this disorder may lie in utero, and be connected to aberrant establishment of the Gut-brain-axis.…”

Section: Discussionmentioning

confidence: 51%

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Prenatal stress disrupts social behavior, cortical neurobiology and commensal microbes in adult male offspring

Gur

Palkar

Rajasekera

et al. 2019

Behavioural Brain Research

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In utero and early neonatal exposure to maternal stress is linked with psychiatric disorders, and the underlying mechanisms are currently being elucidated. We used a prenatal stressor in pregnant mice to examine novel relationships between prenatal stress exposure, changes in the gut microbiome, and social behavior. Here, we show that males exposed to prenatal stress had a significant reduction in social behavior in adulthood, with increased corticosterone release following social interaction. Male offspring exposed to prenatal stress also had neuroinflammation, decreased oxytocin receptor, and decreased serotonin metabolism in their cortex in adulthood, which are linked to decreased social behavior. Finally, we found a significant difference in commensal microbes, including decreases in Bacteroides and Parabacteroides, in adult male offspring exposed to prenatal stress when compared to non-stressed controls. Our findings indicate that gestation is a critical window where maternal stress contributes to the development of aberrant social behaviors and alterations in cortical neurobiology, and that prenatal stress is sufficient to disrupt the male gut-brain axis into adulthood.

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Section: Discussionsupporting

confidence: 79%

Section: Discussionmentioning

confidence: 51%

Prenatal stress disrupts social behavior, cortical neurobiology and commensal microbes in adult male offspring

Gur

Palkar

Rajasekera

et al. 2019

Behavioural Brain Research

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“…Changes in the plasma or serum concentrations and genetic variants of synthesizing enzymes, receptors or transporters in both the 5-HT and DA systems have been reported to co-occur in psychiatric disorders. For example, cerebral monoamine oxidase activity that catalyzes the metabolism of monoamine neurotransmitters, such as 5-HT and DA, was significantly lower by 20.6% in autistic groups compared with that in normal controls [15]. …”

Section: Introductionmentioning

confidence: 99%

Expression of cerebral serotonin related to anxiety-like behaviors in C57BL/6 offspring induced by repeated subcutaneous prenatal exposure to low-dose lipopolysaccharide

et al. 2017

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Prenatal exposure to lipopolysaccharide (LPS), which likely occurs due to infection or contact with environmental allergens during pregnancy, is a proposed risk factor that induces anxiety- and autism spectrum disorder-like behaviors in offspring. However, the molecular and behavioral changes in offspring after maternal immune activation have not been completely identified. We hypothesized that a subcutaneous injection of LPS in a pregnant mouse would induce changes in cerebral serotonin (5-HT) in parallel to the appearance of anxiety-like behaviors in the dam’s offspring. After LPS injections (total, 100 μg/Kg), the time spent in the central region during the open field test and the number of times that the mice moved between the light and dark boxes and between the open and closed arms on the elevated plus maze test revealed anxiety-like behaviors in offspring at 5, 6 and 9 weeks of age. The mRNA expression levels of tph2 (5-HT synthesizing enzyme) and slc6a4 (5-HT transporter) were down-regulated in both adolescent (5 weeks of age) and adult (8 weeks of age) brains. Immunohistochemistry revealed that the numbers and sizes of tph2-expressing cells were notably decreased in the raphe nuclei of the midbrain of adults. Moreover, compared with controls (phosphate-buffered saline-treated offspring), the cerebral 5-HT concentration at adolescence and adulthood in LPS-induced offspring was significantly decreased. We concluded that maternal immune activation induced by exposure to a low dose of LPS decreased cerebral 5-HT levels in parallel to the down-regulation of the tph2 and slc6a4 genes and in conjunction with anxiety-like behaviors in offspring.

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“…Indeed, it has been demonstrated that pre- and postnatal exposure to abnormally high levels of the serotonergic agonist, mimicking the levels observed in autism, induced a significant decrease in the total number of dendritic spines in neurons of the dentate nucleus of rat cerebellum [180]. In addition, analysis of postmortem tissues has revealed a significant impairment in the activity of monoamine oxidases-A (MAO-A), in the cerebellum of children with autism (age 4–12 years) compared to control subjects [181]. Since monoamine oxidases (MAOs) catalyze the metabolism of monoamine neurotransmitters, a reduced MAO-A activity will cause an increase of 5-HT level in the brain of autistic subjects.…”

Section: Discussionmentioning

confidence: 99%

Maturation, Refinement, and Serotonergic Modulation of Cerebellar Cortical Circuits in Normal Development and in Murine Models of Autism

et al. 2017

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The formation of the complex cerebellar cortical circuits follows different phases, with initial synaptogenesis and subsequent processes of refinement guided by a variety of mechanisms. The regularity of the cellular and synaptic organization of the cerebellar cortex allowed detailed studies of the structural plasticity mechanisms underlying the formation of new synapses and retraction of redundant ones. For the attainment of the monoinnervation of the Purkinje cell by a single climbing fiber, several signals are involved, including electrical activity, contact signals, homosynaptic and heterosynaptic interaction, calcium transients, postsynaptic receptors, and transduction pathways. An important role in this developmental program is played by serotonergic projections that, acting on temporally and spatially regulated postsynaptic receptors, induce and modulate the phases of synaptic formation and maturation. In the adult cerebellar cortex, many developmental mechanisms persist but play different roles, such as supporting synaptic plasticity during learning and formation of cerebellar memory traces. A dysfunction at any stage of this process can lead to disorders of cerebellar origin, which include autism spectrum disorders but are not limited to motor deficits. Recent evidence in animal models links impairment of Purkinje cell function with autism-like symptoms including sociability deficits, stereotyped movements, and interspecific communication by vocalization.

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Monoamine oxidase‐A and B activities in the cerebellum and frontal cortex of children and young adults with autism

Cited by 24 publications

References 49 publications

Prenatal stress disrupts social behavior, cortical neurobiology and commensal microbes in adult male offspring

Prenatal stress disrupts social behavior, cortical neurobiology and commensal microbes in adult male offspring

Expression of cerebral serotonin related to anxiety-like behaviors in C57BL/6 offspring induced by repeated subcutaneous prenatal exposure to low-dose lipopolysaccharide

Maturation, Refinement, and Serotonergic Modulation of Cerebellar Cortical Circuits in Normal Development and in Murine Models of Autism

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