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Absence of BRINP1 in mice causes increase of hippocampal neurogenesis and behavioral alterations relevant to human psychiatric disorders.

Kobayashi M, Nakatani T, Koda T, Matsumoto K, Ozaki R, Mochida N, Takao K, Miyakawa T, Matsuoka I - Mol Brain (2014)

Bottom Line: Furthermore, BRINP1-KO mice showed abnormal behaviors with increase in locomotor activity, reduced anxiety-like behavior, poor social interaction, and slight impairment of working memory, all of which resemble symptoms of human psychiatric disorders such as schizophrenia and attention-deficit/hyperactivity disorder (ADHD).Absence of BRINP1 causes deregulation of neurogenesis and impairments of neuronal differentiation in adult hippocampal circuitry.These abnormal behaviors could be caused by alteration of hippocampal circuitry as a consequence of the lack of BRINP1.

View Article: PubMed Central - HTML - PubMed

Affiliation: Laboratory of Physiological Chemistry, College of Pharmaceutical Sciences, Matsuyama University, 4-2 Bunkyo-cho, Matsuyama, Ehime 790-8578, Japan. imatsuok@cc.matsuyama-u.ac.jp.

ABSTRACT

Background: We have previously identified BRINP (BMP/RA-inducible neural-specific protein-1, 2, 3) family genes that possess the ability to suppress cell cycle progression in neural stem cells. Of the three family members, BRINP1 is the most highly expressed in various brain regions, including the hippocampus, in adult mice and its expression in dentate gyrus (DG) is markedly induced by neural activity. In the present study, we generated BRINP1-deficient (KO) mice to clarify the physiological functions of BRINP1 in the nervous system.

Results: Neurogenesis in the subgranular zone of dentate gyrus was increased in BRINP1-KO mice creating a more immature neuronal population in granule cell layer. The number of parvalbumin expressing interneuron in hippocampal CA1 subregion was also increased in BRINP1-KO mice. Furthermore, BRINP1-KO mice showed abnormal behaviors with increase in locomotor activity, reduced anxiety-like behavior, poor social interaction, and slight impairment of working memory, all of which resemble symptoms of human psychiatric disorders such as schizophrenia and attention-deficit/hyperactivity disorder (ADHD).

Conclusions: Absence of BRINP1 causes deregulation of neurogenesis and impairments of neuronal differentiation in adult hippocampal circuitry. Abnormal behaviors comparable to those of human psychiatric disorders such as hyperactivity and poor social behavior were observed in BRINP1-KO mice. These abnormal behaviors could be caused by alteration of hippocampal circuitry as a consequence of the lack of BRINP1.

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Working memory of BRINP1-KO mice in T-maze test. (A) Percentage of correct responses in free-choice run. (B) Latency to complete one session. (C) Distance traveled within one session. (D) Percentage of correct responses when each delay duration was inserted between forced-choice run and free-choice run. (wild-type mice, n = 11; BRINP1-KO mice, n = 9) Error bars indicate SEM.
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Figure 6: Working memory of BRINP1-KO mice in T-maze test. (A) Percentage of correct responses in free-choice run. (B) Latency to complete one session. (C) Distance traveled within one session. (D) Percentage of correct responses when each delay duration was inserted between forced-choice run and free-choice run. (wild-type mice, n = 11; BRINP1-KO mice, n = 9) Error bars indicate SEM.

Mentions: Working memory of mice was assessed by T-maze alteration test. Percentages of correct responses of BRINP1-KO mice were considerably lower than that of wild-type mice at the certain blocks of 3 sessions during repetitive sessions with short delay period (3 s) (Figure 6A). Although BRINP1-KO mice traveled similar distances compared to wild-type mice during the T-maze test (Figure 6C), they performed the test in shorter time than wild-type mice (Figure 6B). When difficulty of the task was raised by prolonging the delay period (≥30 s), BRINP1-KO mice showed lower performances than wild-type mice (Figure 6D). These results suggest that mild impairment of working memory of BRINP1-KO mice became apparent when the difficulty level was raised.


Absence of BRINP1 in mice causes increase of hippocampal neurogenesis and behavioral alterations relevant to human psychiatric disorders.

Kobayashi M, Nakatani T, Koda T, Matsumoto K, Ozaki R, Mochida N, Takao K, Miyakawa T, Matsuoka I - Mol Brain (2014)

Working memory of BRINP1-KO mice in T-maze test. (A) Percentage of correct responses in free-choice run. (B) Latency to complete one session. (C) Distance traveled within one session. (D) Percentage of correct responses when each delay duration was inserted between forced-choice run and free-choice run. (wild-type mice, n = 11; BRINP1-KO mice, n = 9) Error bars indicate SEM.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC3928644&req=5

Figure 6: Working memory of BRINP1-KO mice in T-maze test. (A) Percentage of correct responses in free-choice run. (B) Latency to complete one session. (C) Distance traveled within one session. (D) Percentage of correct responses when each delay duration was inserted between forced-choice run and free-choice run. (wild-type mice, n = 11; BRINP1-KO mice, n = 9) Error bars indicate SEM.
Mentions: Working memory of mice was assessed by T-maze alteration test. Percentages of correct responses of BRINP1-KO mice were considerably lower than that of wild-type mice at the certain blocks of 3 sessions during repetitive sessions with short delay period (3 s) (Figure 6A). Although BRINP1-KO mice traveled similar distances compared to wild-type mice during the T-maze test (Figure 6C), they performed the test in shorter time than wild-type mice (Figure 6B). When difficulty of the task was raised by prolonging the delay period (≥30 s), BRINP1-KO mice showed lower performances than wild-type mice (Figure 6D). These results suggest that mild impairment of working memory of BRINP1-KO mice became apparent when the difficulty level was raised.

Bottom Line: Furthermore, BRINP1-KO mice showed abnormal behaviors with increase in locomotor activity, reduced anxiety-like behavior, poor social interaction, and slight impairment of working memory, all of which resemble symptoms of human psychiatric disorders such as schizophrenia and attention-deficit/hyperactivity disorder (ADHD).Absence of BRINP1 causes deregulation of neurogenesis and impairments of neuronal differentiation in adult hippocampal circuitry.These abnormal behaviors could be caused by alteration of hippocampal circuitry as a consequence of the lack of BRINP1.

View Article: PubMed Central - HTML - PubMed

Affiliation: Laboratory of Physiological Chemistry, College of Pharmaceutical Sciences, Matsuyama University, 4-2 Bunkyo-cho, Matsuyama, Ehime 790-8578, Japan. imatsuok@cc.matsuyama-u.ac.jp.

ABSTRACT

Background: We have previously identified BRINP (BMP/RA-inducible neural-specific protein-1, 2, 3) family genes that possess the ability to suppress cell cycle progression in neural stem cells. Of the three family members, BRINP1 is the most highly expressed in various brain regions, including the hippocampus, in adult mice and its expression in dentate gyrus (DG) is markedly induced by neural activity. In the present study, we generated BRINP1-deficient (KO) mice to clarify the physiological functions of BRINP1 in the nervous system.

Results: Neurogenesis in the subgranular zone of dentate gyrus was increased in BRINP1-KO mice creating a more immature neuronal population in granule cell layer. The number of parvalbumin expressing interneuron in hippocampal CA1 subregion was also increased in BRINP1-KO mice. Furthermore, BRINP1-KO mice showed abnormal behaviors with increase in locomotor activity, reduced anxiety-like behavior, poor social interaction, and slight impairment of working memory, all of which resemble symptoms of human psychiatric disorders such as schizophrenia and attention-deficit/hyperactivity disorder (ADHD).

Conclusions: Absence of BRINP1 causes deregulation of neurogenesis and impairments of neuronal differentiation in adult hippocampal circuitry. Abnormal behaviors comparable to those of human psychiatric disorders such as hyperactivity and poor social behavior were observed in BRINP1-KO mice. These abnormal behaviors could be caused by alteration of hippocampal circuitry as a consequence of the lack of BRINP1.

Show MeSH
Related in: MedlinePlus