Homeostasis of serine enantiomers is disrupted in the post-mortem caudate putamen and cerebrospinal fluid of living Parkinson's disease patients

• Published in: Neurobiology of Disease Vol. 184; p. 106203
• Main Authors: Di Maio, Anna, Nuzzo, Tommaso, Gilio, Luana, Serra, Marcello, Buttari, Fabio, Errico, Francesco, De Rosa, Arianna, Bassi, Mario Stampanoni, Morelli, Micaela, Sasabe, Jumpei, Sulzer, David, Carta, Manolo, Centonze, Diego, Usiello, Alessandro
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.08.2023; Elsevier BV; Elsevier
• Subjects: alanine cysteine serine transporter (SLC1A4); alanine cysteine serine transporter (SLC1A4); Alzheimer's disease; amyotrophic lateral sclerosis; biomarkers; dopamine; ionotropic N-methyl-D-aspartate receptors (NMDAR); serine; synaptic plasticity; Alzheimer Disease; Alzheimer's disease; Alzheimer's disease; Alanine cysteine serine transporter (SLC1A4); Amyotrophic lateral sclerosis; Biomarkers; Dopamine; Ionotropic N-methyl-D-aspartate receptors (NMDAR); Serine; Synaptic plasticity; Amino Acids; amyotrophic lateral sclerosi; amyotrophic lateral sclerosis; biomarker; biomarkers; dopamine; Homeostasis; Humans; ionotropic N-methyl-D-aspartate receptors (NMDAR); N-Methylaspartate; Neurosciences. Biological psychiatry. Neuropsychiatry; Parkinson Disease; Parkinson's disease; Parkinson's disease; alanine cysteine serine transporter (SLC1A4); amyotrophic lateral sclerosis; biomarkers; dopamine; ionotropic N-methyl-D-aspartate receptors (NMDAR); serine; synaptic plasticity; Putamen; RC321-571; Receptors, N-Methyl-D-Aspartate; serine; Settore MED/26 - NEUROLOGIA; synaptic plasticity; serine; OND; BDI; D-Asp; ALS; 6-OHDA; CNS; L-Glu; amyotrophic lateral sclerosis; Aβ; ASCT1; Gly; SFG; MMSE; CSF; L-Asp; UPDRS; PHGDH; Alzheimer's disease; HPLC; SR; AD; D-Ser; biomarkers; ionotropic N-methyl-D-aspartate receptors (NMDAR); CPu; IQR; PMI; DAAO; PD; TH; alanine cysteine serine transporter (SLC1A4); LB; NMDAR; H&Y; synaptic plasticity; L-Ser; MPTP; NMSS; dopamine
• ISSN: 0969-9961; 1095-953X; 1095-953X
• DOI: 10.1016/j.nbd.2023.106203

L-serine generated in astrocytes plays a pivotal role in modulating essential neurometabolic processes, while its enantiomer, D-serine, specifically regulates NMDA receptor (NMDAR) signalling. Despite their physiological relevance in modulating cerebral activity, serine enantiomers metabolism in Parkinson's disease (PD) remains elusive. Using High-Performance Liquid Chromatography (HPLC), we measured D- and L-serine levels along with other amino acids known to modulate NMDAR function, such as L-glutamate, L-aspartate, D-aspartate, and glycine, in the post-mortem caudate putamen (CPu) and superior frontal gyrus (SFG) of PD patients. Moreover, we examined these amino acids in the cerebrospinal fluid (CSF) of de novo living PD, Alzheimer's disease (AD), and amyotrophic lateral sclerosis (ALS) patients versus subjects with other neurological disorders (OND), used as control. We found higher D-serine and L-serine levels in the CPu of PD patients but not in the SFG, a cerebral region that, in contrast to the CPu, is not innervated by nigral dopaminergic terminals. We also highlighted a significant elevation of both serine enantiomers in the CSF samples from PD but not in those of AD and ALS patients, compared with control subjects. By contrast, none or only minor changes were found in the amount of other NMDAR modulating amino acids. Our findings identify D-serine and L-serine level upregulation as a biochemical signature associated with nigrostriatal dopaminergic degeneration in PD. •D-serine and L-serine levels are increased in the CPu and CSF of PD patients.•Clinical features of PD patients are not correlate with CSF D-serine and L-serine levels.•Loss of DA signalling does not alter striatal SR and PHGDH protein expression.•Loss of DA signalling reduced the striatal expression of astrocytic serine transporter ASCT1.