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D1 dopamine receptor antagonists as a new therapeutic strategy to treat autistic-like behaviours in lysosomal storage disorders.
Mol Psychiatry
January 2025
Telethon Institute of Genetics and Medicine, Via Campi Flegrei 34, Pozzuoli, 80078, Naples, Italy.
Lysosomal storage disorders characterized by defective heparan sulfate (HS) degradation, such as Mucopolysaccharidosis type IIIA-D (MPS-IIIA-D), result in neurodegeneration and dementia in children. However, dementia is preceded by severe autistic-like behaviours (ALBs), presenting as hyperactivity, stereotypies, social interaction deficits, and sleep disturbances. The absence of experimental studies on ALBs' mechanisms in MPS-III has led clinicians to adopt symptomatic treatments, such as antipsychotics, which are used for non-genetic neuropsychiatric disorders.
View Article and Find Full Text PDFNuclear calcium signaling in D1 receptor-expressing neurons of the nucleus accumbens regulates molecular, cellular and behavioral adaptations to cocaine.
Biol Psychiatry
January 2025
Institute of Biology Paris-Seine, laboratory Neuroscience Paris-Seine, CNRS, INSERM, Sorbonne Université, UPMC Université Paris 06 F-75005, Paris, France. Electronic address:
Background: The persistence of cocaine-evoked adaptations relies on gene regulations within the reward circuit, especially in the ventral striatum (i.e., nucleus accumbens (NAc)).
View Article and Find Full Text PDFEvidence for direct dopaminergic connections between substantia nigra pars compacta and thalamus in young healthy humans.
Front Neural Circuits
January 2025
Department of Advanced Medical and Surgical Sciences, Advanced MRI Research Center, University of Campania "Luigi Vanvitelli", Naples, Italy.
The substantia nigra pars compacta (SNc), one of the main dopaminergic nuclei of the brain, exerts a regulatory function on the basal ganglia circuitry via the nigro-striatal pathway but its possible dopaminergic innervation of the thalamus has been only investigated in non-human primates. The impossibility of tract-tracing studies in humans has boosted advanced MRI techniques and multi-shell high-angular resolution diffusion MRI (MS-HARDI) has promised to shed more light on the structural connectivity of subcortical structures. Here, we estimated the possible dopaminergic innervation of the human thalamus via an MS-HARDI tractography of the SNc in healthy human young adults.
View Article and Find Full Text PDFNon-motor asymmetry and dopamine degeneration in Parkinson's disease.
Brain Commun
January 2025
Department of Clinical Medicine, Aarhus University Hospital, Aarhus N, 8200 Aarhus, Denmark.
Asymmetric dopaminergic degeneration of the striatum is a characteristic feature of Parkinson's disease, associated with right-left asymmetry in motor function. As such, studying asymmetry provides insights into progressive neurodegeneration between cerebral hemispheres. Given the impact of Lewy pathology on various neurotransmitter systems beyond the dopaminergic, it may be that other neuronal systems in the predominantly affected hemisphere are similarly affected.
View Article and Find Full Text PDFThe class-IIa HDAC inhibitor TMP269 promotes BMP-Smad signalling and is neuroprotective in in vitro and in vivo 6-hydroxydopamine models of Parkinson's disease.
Neuropharmacology
January 2025
Department of Anatomy & Neuroscience, School of Medicine, University College Cork (UCC), Cork, Ireland; APC Microbiome Ireland, UCC, Cork, Ireland. Electronic address:
Degeneration of midbrain nigrostriatal dopaminergic neurons is a pathological hallmark of Parkinson's disease (PD). Peripheral delivery of a compound(s) to arrest or slow this dopaminergic degeneration is a key therapeutic goal. Pan-inhibitors of histone deacetylase (HDAC) enzymes, key epigenetic regulators, have shown therapeutic promise in PD models.
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