5-HT7 receptor activation rescues impaired synaptic plasticity in an autistic-like rat model induced by prenatal VPA exposure

Autor: Shima Davoudi, Razieh Hajisoltani, Maryam Khodaverdi, Narges Hosseinmardi, Gila Behzadi, Zohreh Tavassoli, Mahyar Janahmadi, Mona Rahdar, Zahra Ghasemi, Aeen Ebrahim Amini
Rok vydání: 2021
Předmět:
Autism Spectrum Disorder
GABA Agents
Cognitive Neuroscience
Long-Term Potentiation
Experimental and Cognitive Psychology
Neurotransmission
Serotonergic
Piperazines
050105 experimental psychology
5-HT7 receptor
Elevated Plus Maze Test
03 medical and health sciences
Behavioral Neuroscience
0302 clinical medicine
Neurochemical
Phenols
Pregnancy
Animals
Medicine
0501 psychology and cognitive sciences
Social Behavior
CA1 Region
Hippocampal
5-HT receptor
Sulfonamides
Neuronal Plasticity
Behavior
Animal
business.industry
Valproic Acid
05 social sciences
Excitatory Postsynaptic Potentials
Long-term potentiation
medicine.disease
Rats
Serotonin Receptor Agonists
Disease Models
Animal
Prenatal Exposure Delayed Effects
Receptors
Serotonin
Synaptic plasticity
Raphe Nuclei
Autism
Female
Serotonin Antagonists
business
Open Field Test
Neuroscience
Locomotion
030217 neurology & neurosurgery
Zdroj: Neurobiology of Learning and Memory. 183:107462
ISSN: 1074-7427
DOI: 10.1016/j.nlm.2021.107462
Popis: Autism spectrum disorder (ASD) is a severe life-long neuropsychiatric disorder. Alterations and imbalance of several neurochemical systems may be involved in ASD pathophysiology, of them, serotonergic neurotransmission dysfunction and deficiency may underlie behavioral abnormalities associated with ASD. However, the functional importance of serotonergic receptors, particularly 5HT7 receptors in ASD pathology remains poorly defined. Serotonin receptor subtype 7 (5-HT7R) plays a direct regulatory role in the development and also for the mature function of the brain, therefore, further studies are necessary to elucidate the role of these receptors in the etiology of autism. To address this issue, we combined here behavioral, electrophysiological methods to further characterize the contribution of 5-HT7Rs in the prenatal valproic acid (VPA) exposure-induced impairment in synaptic plasticity and their impact on the associated behavioral changes. This may help to unravel the underlying cellular mechanisms involved in ASD and can lead to new treatment and/or prevention therapies based on the role of the serotonergic system for autism. Findings revealed that compared to control, autistic-like offspring showed increased anxiety-like behavior, reduced social interaction, decreased locomotor activity, and impaired identification of the novel object. However, administration of 5-HT7Rs agonist, LP-211, for 7 consecutive days before testing from postnatal day 21 to 27 reversed all behavioral deficits induced by prenatal exposure to VPA in offspring. Also, both short-term depression and long-term potentiation were impaired in the autistic-like pups, but activation of 5-HT7Rs rescued the LTP impairment in the autistic-like group so that there was no significant difference between the two groups. Blockade of 5-HT7Rs caused LTP impairment following HFS in the autistic-like group. Besides, there was a significant difference in LTD induction following SB-269970 application between the control and the autistic-like groups measured at first 10 min following TPS. Moreover, both the number and the size of retrograde fast blue-labelled neurons in the raphe nuclei were reduced. Overall, these results provide for the first time, as far as we know, functional evidence for the restorative role of 5-HT7Rs activation against prenatal VPA exposure induced behavioral deficits and hippocampal synaptic plasticity impairment. Therefore, these receptors could be a potential and promising pharmacotherapy target for the treatment of autism.
Databáze: OpenAIRE
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