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      Fetal and lactational exposure to the no-observed-adverse-effect level (NOAEL) dose of the neonicotinoid pesticide clothianidin inhibits neurogenesis and induces different behavioral abnormalities at the developmental stages in male mice

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          Abstract

          Recently, it has been reported that neonicotinoid pesticides (NNs) are transferred from mother to child and are assumed to affect the next generation, but the behavioral effects of NN exposure at different developmental stages have not been investigated. We exposed mice to no-observed-adverse-effect level (NOAEL) doses of clothianidin (CLO) during the fetal and lactational period, and then evaluated the neurobehavioral effects in juvenile and adult mice. Significant increases in anxiety-like behavior and locomotor activity were observed in juveniles and adults, respectively, and neuronal activity and neurogenesis in the hippocampal dentate gyrus were affected in both stages. These results suggest that fetal and lactational exposure to CLO may inhibit neurogenesis and cause different behavioral abnormalities at different developmental stages.

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          Most cited references31

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          Critical periods of vulnerability for the developing nervous system: evidence from humans and animal models.

          Vulnerable periods during the development of the nervous system are sensitive to environmental insults because they are dependent on the temporal and regional emergence of critical developmental processes (i.e., proliferation, migration, differentiation, synaptogenesis, myelination, and apoptosis). Evidence from numerous sources demonstrates that neural development extends from the embryonic period through adolescence. In general, the sequence of events is comparable among species, although the time scales are considerably different. Developmental exposure of animals or humans to numerous agents (e.g., X-ray irradiation, methylazoxymethanol, ethanol, lead, methyl mercury, or chlorpyrifos) demonstrates that interference with one or more of these developmental processes can lead to developmental neurotoxicity. Different behavioral domains (e.g., sensory, motor, and various cognitive functions) are subserved by different brain areas. Although there are important differences between the rodent and human brain, analogous structures can be identified. Moreover, the ontogeny of specific behaviors can be used to draw inferences regarding the maturation of specific brain structures or neural circuits in rodents and primates, including humans. Furthermore, various clinical disorders in humans (e.g., schizophrenia, dyslexia, epilepsy, and autism) may also be the result of interference with normal ontogeny of developmental processes in the nervous system. Of critical concern is the possibility that developmental exposure to neurotoxicants may result in an acceleration of age-related decline in function. This concern is compounded by the fact that developmental neurotoxicity that results in small effects can have a profound societal impact when amortized across the entire population and across the life span of humans. Images Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 8 Figure 9 Figure 12 Figure 14 Figure 16 Figure 17
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            Adult hippocampal neurogenesis in depression.

            The development of new treatments for depression is predicated upon identification of neural substrates and mechanisms that underlie its etiology and pathophysiology. The heterogeneity of depression indicates that its origin may lie in dysfunction of multiple brain regions. Here we evaluate adult hippocampal neurogenesis as a candidate mechanism for the etiology of depression and as a substrate for antidepressant action. Current evidence indicates that adult hippocampal neurogenesis may not be a major contributor to the development of depression, but may be required for some of the behavioral effects of antidepressants. We next revisit the functional differentiation of the hippocampus along the septo-temporal axis within the context of adult hippocampal neurogenesis and suggest that neurogenesis in the ventral dentate gyrus may be preferentially involved in regulation of emotion. Finally, we speculate on how increased adult hippocampal neurogenesis may modulate dentate gyrus function to confer the behavioral effects of antidepressants.
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              A role for adult neurogenesis in spatial long-term memory.

              Adult hippocampal neurogenesis has been linked to learning but details of the relationship between neuronal production and memory formation remain unknown. Using low dose irradiation to inhibit adult hippocampal neurogenesis we show that new neurons aged 4-28 days old at the time of training are required for long-term memory in a spatial version of the water maze. This effect of irradiation was specific since long-term memory for a visibly cued platform remained intact. Furthermore, irradiation just before or after water maze training had no effect on learning or long-term memory. Relationships between learning and new neuron survival, as well as proliferation, were investigated but found non-significant. These results suggest a new role for adult neurogenesis in the formation and/or consolidation of long-term, hippocampus-dependent, spatial memories.
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                Author and article information

                Journal
                J Vet Med Sci
                J Vet Med Sci
                JVMS
                The Journal of Veterinary Medical Science
                The Japanese Society of Veterinary Science
                0916-7250
                1347-7439
                01 February 2021
                March 2021
                : 83
                : 3
                : 542-548
                Affiliations
                [1) ]Laboratory of Animal Molecular Morphology, Department of Animal Science, Graduate School of Agricultural Science, Kobe University, 1-1 Rokkodai, Nada, Kobe, Hyogo 657-8501, Japan
                [2) ]Laboratory of Histophysiology, Department of Animal Science, Graduate School of Agricultural Science, Kobe University, 1-1 Rokkodai, Nada, Kobe, Hyogo 657-8501, Japan
                [3) ]Life Science Research Center, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan
                [4) ]Laboratory of Toxicology, Department of Environmental Veterinary Sciences, Faculty of Veterinary Medicine, Hokkaido University, Kita 18, Nishi 9, Kita-ku, Sapporo, Hokkaido 060-0818, Japan
                [5) ]Water Research Group, Unit for Environmental Sciences and Management, North-West University, Potchefstroom, South Africa
                Author notes
                [* ]Correspondence to: Hoshi, N.: nobhoshi@ 123456kobe-u.ac.jp
                Article
                20-0721
                10.1292/jvms.20-0721
                8025408
                33518607
                8994de02-0818-4977-a692-e93260c9610f
                ©2021 The Japanese Society of Veterinary Science

                This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives (by-nc-nd) License. (CC-BY-NC-ND 4.0: https://creativecommons.org/licenses/by-nc-nd/4.0/ )

                History
                : 21 December 2020
                : 19 January 2021
                Categories
                Toxicology
                Note

                behavioral test,clothianidin,developmental stage,fetal and lactational exposure,neurogenesis

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