Picolinic Acid is an endogenous metabolite of L-tryptophan (TRP) that has been reported to possess a wide range of neuroprotective, immunological, and anti-proliferative affects within the body. However the salient physiological function of this molecule is yet to be established. The synthesis of picolinic acid as a product of the kynurenine pathway (KP) suggests that, similar to other KP metabolites, picolinic acid may play a role in the pathogenesis of infl ammatory disorders within the CNS and possibly other organs.In this paper we review the limited body of literature dealing with the physiological actions of picolinic acid in the CNS and its associated synthesis via the kynurenine pathway in health and disease. Discrepancies and gaps in our current knowledge of picolinic acid are identifi ed highlighting areas of research to promote a more complete understanding of its endogenous function in the brain.

Amyotrophic lateral sclerosis (ALS) is a progressive and fatal motor neuron disease of unknown pathogenesis. The kynurenine pathway (KP), activated during neuroinflammation, is emerging as a possible contributory factor in ALS. The KP is the major route for tryptophan (TRP) catabolism. The intermediates generated can be either neurotoxic, such as quinolinic acid (QUIN), or neuroprotective, such as picolinic acid (PIC), an important endogenous chelator. The first and inducible enzyme of the pathway is indoleamine 2,3-dioxygenase (IDO). The present study aimed to characterize the expression of the KP in cerebrospinal fluid (CSF), serum and central nervous system (CNS) tissue of ALS patients. Using high performance liquid chromatography, we analysed the levels of TRP and kynurenine (KYN), and, with gas chromatography/mass spectrometry, the levels of PIC and QUIN, in the CSF and serum of ALS patients and control subjects. Immunohistochemistry was employed to determine the expression of QUIN, IDO and human leukocyte antigen-DR (HLA-DR) in sections of brain and spinal cord from ALS patients. There were significantly increased levels of CSF and serum TRP (P < 0.0001), KYN (P < 0.0001) and QUIN (P < 0.05) and decreased levels of serum PIC (P < 0.05) in ALS samples. There was a significant increase in activated microglia expressing HLA-DR (P < 0.0001) and increased neuronal and microglial expression of IDO and QUIN in ALS motor cortex and spinal cord. We show the presence of neuroinflammation in ALS and provide the first strong evidence for the involvement of the KP in ALS. These data point to an inflammation-driven excitotoxic-chelation defective mechanism in ALS, which may be amenable to inhibitors of the KP.

BackgroundGross motor skills are fundamental to childhood development. The effectiveness of current physical therapy options for children with mild to moderate gross motor disorders is unknown. The aim of this study was to systematically review the literature to investigate the effectiveness of conservative interventions to improve gross motor performance in children with a range of neurodevelopmental disorders.MethodsA systematic review with meta-analysis was conducted. MEDLINE, EMBASE, AMED, CINAHL, PsycINFO, PEDro, Cochrane Collaboration, Google Scholar databases and clinical trial registries were searched. Published randomised controlled trials including children 3 to ≤18 years with (i) Developmental Coordination Disorder (DCD) or Cerebral Palsy (CP) (Gross Motor Function Classification System Level 1) or Developmental Delay or Minimal Acquired Brain Injury or Prematurity (<30 weeks gestational age) or Fetal Alcohol Spectrum Disorders; and (ii) receiving non-pharmacological or non-surgical interventions from a health professional and (iii) gross motor outcomes obtained using a standardised assessment tool. Meta-analysis was performed to determine the pooled effect of intervention on gross motor function. Methodological quality and strength of meta-analysis recommendations were evaluated using PEDro and the GRADE approach respectively.ResultsOf 2513 papers, 9 met inclusion criteria including children with CP (n = 2) or DCD (n = 7) receiving 11 different interventions. Only two of 9 trials showed an effect for treatment. Using the least conservative trial outcomes a large beneficial effect of intervention was shown (SMD:-0.8; 95% CI:-1.1 to −0.5) with “very low quality” GRADE ratings. Using the most conservative trial outcomes there is no treatment effect (SMD:-0.1; 95% CI:-0.3 to 0.2) with “low quality” GRADE ratings. Study limitations included the small number and poor quality of the available trials.ConclusionAlthough we found that some interventions with a task-orientated framework can improve gross motor outcomes in children with DCD or CP, these findings are limited by the very low quality of the available evidence. High quality intervention trials are urgently needed.Electronic supplementary materialThe online version of this article (doi:10.1186/s12887-016-0731-6) contains supplementary material, which is available to authorized users.