P.409 Working memory impairment in dopamine transporter knockout rats

Kurzina, Natalia; Aristova, Irina; Volnova, Anna; Gainetdinov, Raul R.

doi:10.1016/j.euroneuro.2019.09.422

Cited by 2 publications

(3 citation statements)

References 2 publications

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“…DAT-knockout rats show impairment in learning the cognitive task, however, their hyperactivity does not prevent the capability to learn a non-spatial cognitive task in the appearance of novel stimuli (Kurzina et al, 2021). Importantly, DAT genetic hypofunction in mice produced alterations consistent with ADHD, but not with schizophrenia or bipolar disorders (Mereu et al, 2017) in one study, but it was shown in another study that DAT silencing in the rat produces abnormalities in the prefrontal-midbrain and in striato-cerebellar circuits leading to motor hyperactivity and compulsive-like behaviors applicable for ADHD, schizophrenia, and obsessive-compulsive disorder (Reinwald et al, 2022).…”

Section: Dat1mentioning

confidence: 94%

Attention-deficit/hyperactive disorder updates

Kessi

Duan

Xiong

et al. 2022

Front. Mol. Neurosci.

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BackgroundAttention-deficit/hyperactive disorder (ADHD) is a neurodevelopmental disorder that commonly occurs in children with a prevalence ranging from 3.4 to 7.2%. It profoundly affects academic achievement, well-being, and social interactions. As a result, this disorder is of high cost to both individuals and society. Despite the availability of knowledge regarding the mechanisms of ADHD, the pathogenesis is not clear, hence, the existence of many challenges especially in making correct early diagnosis and provision of accurate management.ObjectivesWe aimed to review the pathogenic pathways of ADHD in children. The major focus was to provide an update on the reported etiologies in humans, animal models, modulators, therapies, mechanisms, epigenetic changes, and the interaction between genetic and environmental factors.MethodsReferences for this review were identified through a systematic search in PubMed by using special keywords for all years until January 2022.ResultsSeveral genes have been reported to associate with ADHD: DRD1, DRD2, DRD4, DAT1, TPH2, HTR1A, HTR1B, SLC6A4, HTR2A, DBH, NET1, ADRA2A, ADRA2C, CHRNA4, CHRNA7, GAD1, GRM1, GRM5, GRM7, GRM8, TARBP1, ADGRL3, FGF1, MAOA, BDNF, SNAP25, STX1A, ATXN7, and SORCS2. Some of these genes have evidence both from human beings and animal models, while others have evidence in either humans or animal models only. Notably, most of these animal models are knockout and do not generate the genetic alteration of the patients. Besides, some of the gene polymorphisms reported differ according to the ethnic groups. The majority of the available animal models are related to the dopaminergic pathway. Epigenetic changes including SUMOylation, methylation, and acetylation have been reported in genes related to the dopaminergic pathway.ConclusionThe dopaminergic pathway remains to be crucial in the pathogenesis of ADHD. It can be affected by environmental factors and other pathways. Nevertheless, it is still unclear how environmental factors relate to all neurotransmitter pathways; thus, more studies are needed. Although several genes have been related to ADHD, there are few animal model studies on the majority of the genes, and they do not generate the genetic alteration of the patients. More animal models and epigenetic studies are required.

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Section: Dat1mentioning

confidence: 94%

Attention-deficit/hyperactive disorder updates

Kessi

Duan

Xiong

et al. 2022

Front. Mol. Neurosci.

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“…Altered levels of these dopamine-signal terminators can also impact cognition, as observed with the DAT inhibitors that improve memory and cognition in neurodegenerative diseases (as described below). Paradoxically, lower dopamine transporter levels have been observed in some psychiatric disorders, such as attention deficit hyperactivity disorder (Kurzina et al, 2020) and depression (Pizzagalli et al, 2019;Dubol et al, 2020). This paucity of dopamine in the absence of higher dopamine transporter in these disorders may be due to high extracellular levels of dopamine that eventually lead to an inability to replenish dopamine in synaptic vesicles, causing a lower amplitude of dopamine release per nerve impulse (Benoit-Marand et al, 2000).…”

Section: Mesocorticolimbic Circuitry: the Interplay Of Dopamine And T...mentioning

confidence: 99%

“…However, its reduced levels in the NS loop are linked with cognitive impairment (Li et al, 2020;Fiorenzato et al, 2021). The DAT is found to be closely associated with cognition, as the uninhibited blockade or elimination of the DAT may worsen the disease pathology, as observed in DAT knock-out rodents showing severe cognitive deficits (Leo et al, 2018;Kurzina et al, 2020). Therefore, controlled inhibition of DAT function is crucial to avoid disturbing its physiological effects in the AD brain.…”

Section: Mesocorticolimbic Circuitry: the Interplay Of Dopamine And T...mentioning

confidence: 99%

Targeting dopamine transporter to ameliorate cognitive deficits in Alzheimer's disease

Shaikh,

Ahmad,

Teoh

et al. 2023

Front. Cell. Neurosci.

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Alzheimer's disease (AD) is characterized by the pathologic deposition of amyloid and neurofibrillary tangles in the brain, leading to neuronal damage and defective synapses. These changes manifest as abnormalities in cognition and behavior. The functional deficits are also attributed to abnormalities in multiple neurotransmitter systems contributing to neuronal dysfunction. One such important system is the dopaminergic system. It plays a crucial role in modulating movement, cognition, and behavior while connecting various brain areas and influencing other neurotransmitter systems, making it relevant in neurodegenerative disorders like AD and Parkinson's disease (PD). Considering its significance, the dopaminergic system has emerged as a promising target for alleviating movement and cognitive deficits in PD and AD, respectively. Extensive research has been conducted on dopaminergic neurons, receptors, and dopamine levels as critical factors in cognition and memory in AD. However, the exact nature of movement abnormalities and other features of extrapyramidal symptoms are not fully understood yet in AD. Recently, a previously overlooked element of the dopaminergic system, the dopamine transporter, has shown significant promise as a more effective target for enhancing cognition while addressing dopaminergic system dysfunction in AD.

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P.409 Working memory impairment in dopamine transporter knockout rats

Cited by 2 publications

References 2 publications

Attention-deficit/hyperactive disorder updates

Attention-deficit/hyperactive disorder updates

Targeting dopamine transporter to ameliorate cognitive deficits in Alzheimer's disease

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