Nervous System Deletion of Mammalian INDY in Mice Mimics Dietary Restriction-Induced Memory Enhancement

2020 ◽  
Vol 76 (1) ◽  
pp. 50-56
Author(s):  
Shou-Zen Fan ◽  
Chih-Wei Sung ◽  
Yi-Hsuan Tsai ◽  
Sheng-Rong Yeh ◽  
Wei-Sheng Lin ◽  
...  
Keyword(s):  
Nervous System ◽  
Dietary Restriction ◽  
Motor Coordination ◽  
Granule Cells ◽  
Memory Performance ◽  
Memory Function ◽  
Critical Role ◽  
Hippocampal Neurogenesis ◽  
Physiological Status ◽  
Specific Deletion

Abstract Reduced expression of the Indy (I’m Not Dead Yet) gene extends life span in Caenorhabditis elegans and Drosophila melanogaster and improves the metabolic heath of Mus musculus through inducing a physiological status akin to dietary restriction (DR). Although the function of Indy in aging and hepatic metabolism has been extensively studied, its role in the mouse nervous system remains unclear. Here, we explore the effect of mammalian Indy (mIndy, SLC13A5) gene deletion on murine cognitive function. Similar to what is seen in DR animals, systemic deletion of the mIndy gene (mIndy knockout [KO]) significantly improves memory performance and motor coordination of mice. Both DR and mIndy KO mice act normally in other behavioral tasks, including emotional, social, and food-seeking behaviors. Moreover, we find that tissue-specific deletion of mIndy in the nervous system is sufficient to improve memory performance, while liver-specific deletion has no effect on memory, and results in tests of motor coordination show no changes in either mutant. Mice with systemic or nervous system deletion of mIndy also exhibit increased hippocampal neurogenesis and dendritic spine formation in dentate granule cells; these changes are well-documented contributors to enhanced memory performance. Together, our studies demonstrate a critical role for brain-derived mIndy expression in the regulation of memory function in animals.

scholarly journals An increase in VGF expression through a rapid, transcription-independent, autofeedback mechanism improves cognitive function

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Wei-Jye Lin ◽  
Yan Zhao ◽  
Zhe Li ◽  
Shuyu Zheng ◽  
Jin-lin Zou ◽  
...  
Keyword(s):  
Cognitive Function ◽  
Memory Performance ◽  
Memory Function ◽  
Critical Role ◽  
General Mechanism ◽  
Memory Training ◽  
Translational Efficiency ◽  
Truncation Mutant ◽  
Reporter Assays ◽  
Dependent Learning

AbstractThe release of neuropeptides from dense core vesicles (DCVs) modulates neuronal activity and plays a critical role in cognitive function and emotion. The granin family is considered a master regulator of DCV biogenesis and the release of DCV cargo molecules. The expression of the VGF protein (nonacronymic), a secreted neuropeptide precursor that also belongs to the extended granin family, has been previously shown to be induced in the brain by hippocampus-dependent learning, and its downregulation is mechanistically linked to neurodegenerative diseases such as Alzheimer’s disease and other mood disorders. Currently, whether changes in translational efficiency of Vgf and other granin mRNAs may be associated and regulated with learning associated neural activity remains largely unknown. Here, we show that either contextual fear memory training or the administration of TLQP-62, a peptide derived from the C-terminal region of the VGF precursor, acutely increases the translation of VGF and other granin proteins, such as CgB and Scg2, via an mTOR-dependent signaling pathway in the absence of measurable increases in mRNA expression. Luciferase-based reporter assays confirmed that the 3′-untranslated region (3′UTR) of the Vgf mRNA represses VGF translation. Consistently, the truncation of the endogenous Vgf mRNA 3′UTR results in substantial increases in VGF protein expression both in cultured primary neurons and in brain tissues from knock in mice expressing a 3′UTR-truncation mutant encoded by the modified Vgf gene. Importantly, Vgf 3′UTR-truncated mice exhibit enhanced memory performance and reduced anxiety- and depression-like behaviors. Our results therefore reveal a rapid, transcription-independent induction of VGF and other granin proteins after learning that are triggered by the VGF-derived peptide TLQP-62. Our findings suggest that the rapid, positive feedforward increase in the synthesis of granin family proteins might be a general mechanism to replenish DCV cargo molecules that have been released in response to neuronal activation and is crucial for memory function and mood stability.

scholarly journals Inhibition of Hippocampal Aromatization Impairs Spatial Memory Performance in a Male Songbird

Endocrinology ◽  
2013 ◽  
Vol 154 (12) ◽  
pp. 4707-4714 ◽  
Author(s):  
David J. Bailey ◽  
Chunqi Ma ◽  
Kiran K. Soma ◽  
Colin J. Saldanha
Keyword(s):  
Spatial Memory ◽  
Zebra Finch ◽  
Memory Performance ◽  
Memory Function ◽  
Critical Role ◽  
Electrophysiological Response ◽  
Local Inhibition ◽  
Estradiol Synthesis ◽  
Adjacent Brain

Recent studies have revealed the presence and regulation of aromatase at the vertebrate synapse, and identified a critical role played by presynaptic estradiol synthesis in the electrophysiological response to auditory and other social cues. However, if and how synaptic aromatization affects behavior remains to be directly tested. We have exploited 3 characteristics of the zebra finch hippocampus (HP) to test the role of synaptocrine estradiol provision on spatial memory function. Although the zebra finch HP contains abundant aromatase transcripts and enzyme activity, immunocytochemical studies reveal widespread pre- and postsynaptic, but sparse to undetectable somal, localization of this enzyme. Further, the superficial location of the avian HP makes possible the more exclusive manipulation of its neurochemical characteristics without perturbation of the neuropil and the resultant induction of astroglial aromatase. Last, as in other vertebrates, the HP is critical for spatial memory performance in this species. Here we report that local inhibition of hippocampal aromatization impairs spatial memory performance in an ecologically valid food-finding task. Local aromatase inhibition also resulted in lower levels of estradiol in the HP, but not in adjacent brain areas, and was achieved without the induction of astroglial aromatase. The observed decrement in acquisition and subsequent memory performance as a consequence of lowered aromatization was similar to that achieved by lesioning this locus. Thus, hippocampal aromatization, much of which is achieved at the synapse in this species, is critical for spatial memory performance.

scholarly journals Dlic1 deletion impaired cerebellar development in mouse

2017 ◽  
Author(s):  
Shanshan Kong ◽  
Wufan Tao
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Purkinje Cells ◽  
Motor Coordination ◽  
Granule Cells ◽  
Cytoplasmic Dynein ◽  
Normal Function ◽  
Cerebellar Development ◽  
Protein Levels ◽  
Intermediate Chain

AbstractThe cerebellum is an important model system to study Central Nervous System, it has a striking morphology consisting of folia separated by fissures of different lengths, and the molecules controlling the process of cerebellar development have been unclear. In this study, we report an unrecognized contribution of Dlic1 to the postnatal development of murine cerebellum. Dlic1 encodes a light intermediate chain of cytoplasmic dynein 1, it is a subunit unique to the cytoplasmic form of dynein, and how it contributes to dynein function is not fully understood. Our data show that Dlic1 deletion leads to impaired cerebellar development, foliation and fissuration, the volume of the cerebellum was evidently reduced. Consistent with the histological defects, Dlic1 knockout mice show defective motor coordination, this strongly indicates the fundamental role of Dlic1 in cerebellar development and function. Purkinje cells are located within the cerebellum and form synapses with granule cells. In Dlic1-/- mice, Purkinje cells display reduced dendritic complexity and the distribution of dynein in Purkinje cell layer is changed. We also found that Dlic1 deletion reduced the protein levels of dynein subunits and leads to the defective assembling of dynein subunits. These data indicate that Dlic1 may affect cerebellar development through affecting the normal function of dynein.AbbreviationsDlic1cytoplasmic dynein 1 light intermediate chainCNScentral nervous systemMEFmouse embryo fibroblast

Impact of Comorbid Depression on Serial Position Effects in Alzheimer’s Disease

GeroPsych ◽  
2014 ◽  
Vol 27 (4) ◽  
pp. 161-169 ◽  
Author(s):  
Nienke A. Hofrichter ◽  
Sandra Dick ◽  
Thomas G. Riemer ◽  
Carsten Schleussner ◽  
Monique Goerke ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Serial Position ◽  
Episodic Memory ◽  
Memory Performance ◽  
Memory Function ◽  
Word List ◽  
Position Effects ◽  
Serial Position Effects ◽  
List Memory

Hippocampal dysfunction and deficits in episodic memory have been reported for both Alzheimer’s disease (AD) and major depressive disorder (MDD). Primacy performance has been associated with hippocampus-dependent episodic memory, while recency may reflect working memory performance. In this study, serial position profiles were examined in a total of 73 patients with MDD, AD, both AD and MDD, and healthy controls (HC) by means of CERAD-NP word list memory. Primacy performance was most impaired in AD with comorbid MDD, followed by AD, MDD, and HC. Recency performance, on the other hand, was comparable across groups. These findings indicate that primacy in AD is impaired in the presence of comorbid MDD, suggesting additive performance decrements in this specific episodic memory function.

Introduction to the cognitive abilities account for the reminiscence bump in the temporal distribution of autobiographical memory

2019 ◽  
Author(s):  
Steve M. J. Janssen
Keyword(s):  
Autobiographical Memory ◽  
Cognitive Abilities ◽  
Memory Performance ◽  
Memory Function ◽  
Early Adulthood ◽  
Temporal Distribution ◽  
Alternative Account ◽  
Reminiscence Bump ◽  
Significant Events ◽  
Cue Words

People tend to recall more specific personal events from adolescence and early adulthood than from other lifetime periods, a finding known as the reminiscence bump. Several explanations have suggested that events from the reminiscence bump are especially emotional, important, or positive, but studies using cue words have not found support for these claims. An alternative account postulates that cognitive abilities function optimally in adolescence and early adulthood, which may cause more memories to be stored in those lifetime periods. Although other studies have previously discussed the cognitive abilities account as a possible explanation for the reminiscence bump, it was only recently shown that cognitive abilities are indeed related to autobiographical memory performance. When this recent finding is combined with previous findings that cognitive abilities as well as autobiographical memory function optimally in adolescence and early adulthood, they suggest that the cognitive abilities account is a promising explanation for the reminiscence bump in the temporal distribution of word-cued memories. However, because the account does not aim to explain the reminiscence bump in the distribution of highly significant events, it should be regarded as complementary to the existing accounts.

Heterogeneity and Proliferative and Differential Regulators of NG2-glia in Physiological and Pathological States

2020 ◽  
Vol 27 (37) ◽  
pp. 6384-6406 ◽  
Author(s):  
Zuo Zhang ◽  
Hongli Zhou ◽  
Jiyin Zhou
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Physiological State ◽  
Critical Role ◽  
Adult Brain ◽  
Pathological State ◽  
Peripheral Neurons ◽  
Neuronal Synapses ◽  
The Central Nervous System ◽  
Rapid Modulation

NG2-glia, also called Oligodendrocyte Precursor Cells (OPCs), account for approximately 5%-10% of the cells in the developing and adult brain and constitute the fifth major cell population in the central nervous system. NG2-glia express receptors and ion channels involved in rapid modulation of neuronal activities and signaling with neuronal synapses, which have functional significance in both physiological and pathological states. NG2-glia participate in quick signaling with peripheral neurons via direct synaptic touches in the developing and mature central nervous system. These distinctive glia perform the unique function of proliferating and differentiating into oligodendrocytes in the early developing brain, which is critical for axon myelin formation. In response to injury, NG2-glia can proliferate, migrate to the lesions, and differentiate into oligodendrocytes to form new myelin sheaths, which wrap around damaged axons and result in functional recovery. The capacity of NG2-glia to regulate their behavior and dynamics in response to neuronal activity and disease indicate their critical role in myelin preservation and remodeling in the physiological state and in repair in the pathological state. In this review, we provide a detailed summary of the characteristics of NG2-glia, including their heterogeneity, the regulators of their proliferation, and the modulators of their differentiation into oligodendrocytes.

scholarly journals PKA-RIIβ autophosphorylation modulates PKA activity and seizure phenotypes in mice

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Jingliang Zhang ◽  
Chenyu Zhang ◽  
Xiaoling Chen ◽  
Bingwei Wang ◽  
Weining Ma ◽  
...  
Keyword(s):  
Therapeutic Target ◽  
Neurological Disorders ◽  
Neuronal Excitability ◽  
Granule Cells ◽  
Critical Role ◽  
Intrinsic Excitability ◽  
Seizure Susceptibility ◽  
Seizure Onset ◽  
Potential Therapeutic Target ◽  
Seizure Model

AbstractTemporal lobe epilepsy (TLE) is one of the most common and intractable neurological disorders in adults. Dysfunctional PKA signaling is causally linked to the TLE. However, the mechanism underlying PKA involves in epileptogenesis is still poorly understood. In the present study, we found the autophosphorylation level at serine 114 site (serine 112 site in mice) of PKA-RIIβ subunit was robustly decreased in the epileptic foci obtained from both surgical specimens of TLE patients and seizure model mice. The p-RIIβ level was negatively correlated with the activities of PKA. Notably, by using a P-site mutant that cannot be autophosphorylated and thus results in the released catalytic subunit to exert persistent phosphorylation, an increase in PKA activities through transduction with AAV-RIIβ-S112A in hippocampal DG granule cells decreased mIPSC frequency but not mEPSC, enhanced neuronal intrinsic excitability and seizure susceptibility. In contrast, a reduction of PKA activities by RIIβ knockout led to an increased mIPSC frequency, a reduction in neuronal excitability, and mice less prone to experimental seizure onset. Collectively, our data demonstrated that the autophosphorylation of RIIβ subunit plays a critical role in controlling neuronal and network excitabilities by regulating the activities of PKA, providing a potential therapeutic target for TLE.

scholarly journals Multilab Direct Replication of Flavell, Beach, and Chinsky (1966): Spontaneous Verbal Rehearsal in a Memory Task as a Function of Age

2021 ◽  
Vol 4 (2) ◽  
pp. 251524592110181
Author(s):  
Emily M. Elliott ◽  
Candice C. Morey ◽  
Angela M. AuBuchon ◽  
Nelson Cowan ◽  
Chris Jarrold ◽  
...  
Keyword(s):  
Cognitive Development ◽  
Young Children ◽  
Memory Performance ◽  
Critical Role ◽  
Memory Task ◽  
Older Children ◽  
Continuous Increase ◽  
Verbal Rehearsal ◽  
Picture Memory ◽  
Spontaneous Production

Work by Flavell, Beach, and Chinsky indicated a change in the spontaneous production of overt verbalization behaviors when comparing young children (age 5) with older children (age 10). Despite the critical role that this evidence of a change in verbalization behaviors plays in modern theories of cognitive development and working memory, there has been only one other published near replication of this work. In this Registered Replication Report, we relied on researchers from 17 labs who contributed their results to a larger and more comprehensive sample of children. We assessed memory performance and the presence or absence of verbalization behaviors of young children at different ages and determined that the original pattern of findings was largely upheld: Older children were more likely to verbalize, and their memory spans improved. We confirmed that 5- and 6-year-old children who verbalized recalled more than children who did not verbalize. However, unlike Flavell et al., substantial proportions of our 5- and 6-year-old samples overtly verbalized at least sometimes during the picture memory task. In addition, continuous increase in overt verbalization from 7 to 10 years old was not consistently evident in our samples. These robust findings should be weighed when considering theories of cognitive development, particularly theories concerning when verbal rehearsal emerges and relations between speech and memory.

scholarly journals The laterodorsal tegmentum-ventral tegmental area circuit controls depression-like behaviors by activating ErbB4 in DA neurons

2021 ◽  
Author(s):  
Hongsheng Wang ◽  
Wanpeng Cui ◽  
Wenbing Chen ◽  
Fang Liu ◽  
Zhaoqi Dong ◽  
...  
Keyword(s):  
Ventral Tegmental Area ◽  
Molecular Mechanisms ◽  
Critical Role ◽  
Coping With Stress ◽  
Chemical Genetic ◽  
Chronic Social Defeat Stress ◽  
Ventral Tegmental ◽  
Laterodorsal Tegmentum ◽  
Specific Deletion

AbstractDopamine (DA) neurons in the ventral tegmental area (VTA) are critical to coping with stress. However, molecular mechanisms regulating their activity and stress-induced depression were not well understood. We found that the receptor tyrosine kinase ErbB4 in VTA was activated in stress-susceptible mice. Deleting ErbB4 in VTA or in DA neurons, or chemical genetic inhibition of ErbB4 kinase activity in VTA suppressed the development of chronic social defeat stress (CSDS)-induced depression-like behaviors. ErbB4 activation required the expression of NRG1 in the laterodorsal tegmentum (LDTg); LDTg-specific deletion of NRG1 inhibited depression-like behaviors. NRG1 and ErbB4 suppressed potassium currents of VTA DA neurons and increased their firing activity. Finally, we showed that acute inhibition of ErbB4 after stress attenuated DA neuron hyperactivity and expression of depression-like behaviors. Together, these observations demonstrate a critical role of NRG1-ErbB4 signaling in regulating depression-like behaviors and identify an unexpected mechanism by which the LDTg-VTA circuit regulates the activity of DA neurons.

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