PXD038471-1

PXD038471 is an original dataset announced via ProteomeXchange.

Title	Chronic haloperidol treatment leads to an imbalance of synaptic excitation and inhibition of D1-MSN neurons pointing to a slow remodelling process
Description	Schizophrenia is a chronic mental illness that is among the world’s top twenty causes of years lost to disability according to the global burden of disease 2019 (10.1016/S0140-6736(20)30925-9). Positive symptoms, including hallucinations and delusions in schizophrenia, often improved with conventional antipsychotic medication, which exerts its therapeutic effects mainly by antagonizing the dopamine D2 receptors. Haloperidol was one of the first antipsychotics to be approved by the FDA, and it is since then widely used for the treatment of psychotic disorders including schizophrenia. Despite its high affinity for dopamine D2 receptors, it has been shown that haloperidol interacts with other receptors, such as dopamine D3 and D4 receptors, α-adrenergic receptor 1 and to some extent 5HT2A. Dopaminergic dysfunction is known for decades to be involved in the pathophysiology of schizophrenia, but only recently has the striatum been implicated in such devasting disorder. The dorsal striatum is a brain region involved in motor, cognitive and motivational functions, highly impacted by antipsychotic drugs. Particularly, it is well-recognized that chronic haloperidol administration has a tremendous impact on striatal synaptic plasticity, by changing the volume of dorsal striatum, the number of striatal neurons and the synaptic morphology, both in humans and rodents. Despite the overwhelming evidence correlating chronic haloperidol administration with striatum alterations, so far, the exact striatal synaptic mechanism by which haloperidol exerts its beneficial effects remains unclear. Although dopamine D2 receptor blockade can be achieved within hours after haloperidol administration, the onset of action is delayed by weeks. Thus, it is crucial to better understand the neuronal mechanism behind the delayed clinical effects of haloperidol to improve the treatment outcome. Using proteomic analysis and whole-cell patch-clamp recordings (Figure 1), we demonstrate for the first time a possible mechanism by which haloperidol may be contributing to its beneficial long-term therapeutic effect. Specifically, we demonstrate that modulation of D2-MSNs by chronic haloperidol administration leads to a slow remodeling of D1-neurons that may be responsible for its positive therapeutic effects.
HostingRepository	PRIDE
AnnounceDate	2023-10-24
AnnouncementXML	Submission_2023-10-24_11:35:17.787.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	CátiaSanta
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	S-carboxamidoethyl-L-cysteine
Instrument	TripleTOF 5600

Revision	Datetime	Status	ChangeLog Entry
0	2022-12-01 01:15:23	ID requested
⏵ 1	2023-10-24 11:35:18	announced
2	2023-11-14 09:08:00	announced	2023-11-14: Updated project metadata.

Santa C, Rodrigues D, Coelho JF, Anjo SI, Mendes VM, Bessa-Neto D, Dunn MJ, Cotter D, Baltazar G, Monteiro P, Manadas B, Chronic treatment with D2-antagonist haloperidol leads to inhibitory/excitatory imbalance in striatal D1-neurons. Transl Psychiatry, 13(1):312(2023) [pubmed]

submitter keyword: MSN,Haloperidol, Proteomics

BrunoManadas
contact affiliation	Center for Neuroscience and Cell Biology of theUniversity of Coimbra
contact email	bmanadas@gmail.com
lab head
CátiaSanta
contact affiliation	Center for Neuroscience and Cell Biology
contact email	catiajmsanta@gmail.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD038471
     1. Label: PRIDE project
     2. Name: Chronic haloperidol treatment leads to an imbalance of synaptic excitation and inhibition of D1-MSN neurons pointing to a slow remodelling process