Prevalence of major depressive disorder and its associated factors among adult patients with neurolathyrism in Dawunt District, Ethiopia; 2022: community-based cross-sectional study.

INTRODUCTION: Major Depressive Disorder (MDD) is one of the commonest mental disorders affecting more than 250 million people globally. Patients with chronic illnesses had higher risks for developing MDD than the general population. Neurolathyrism is a chronic illness characterized by lifelong incurable spastic paralysis of lower extremities; causing permanent disability. It is highly prevalent in Dawunt district, Ethiopia; with a point prevalence of 2.4%. Despite this, there were no previous studies assessing the prevalence of MDD among patients with neurolathyrism in Ethiopia. OBJECTIVE: To assess the prevalence of MDD and to identify its associated factors among patients with neurolathyrism in Dawunt district, Ethiopia. METHODS: A community based cross-sectional study was conducted on 260 samples in Dawunt district from February 01 to March 30/ 2021. Multistage sampling technique was used to select study participants. The patient Health Questionnaire-9 (PHQ-9) depression screening tool was used to diagnose MDD. PHQ-9 is a standardized depression screening tool and a PHQ-9 score of ≥ 10 has a sensitivity and specificity of 88.0% [95% CI (83.0-92.0%)] and 85.0% [95% CI (82.0-88.0%)] for screening MDD. Data were collected by interview; entered to EpiData version 4.2.0; exported to SPSS version 25.0 for analysis; descriptive statistics and binary logistic regression model were used; AOR with 95% CI was used to interpret the associations; and finally results were presented by texts, charts, graphs, and tables. RESULTS: A total of 256 adult patients with neurolathyrism were participated; and the prevalence of MDD was found to be 38.7%. Being female [AOR = 3.00; 95% CI (1.15, 7.84)], living alone [AOR = 2.77; 95% CI (1.02-7.53)], being on neurolathyrism stage-3 [AOR = 3.22; 95% CI (1.09, 9.54)] or stage-4 [AOR = 4.00; 95% CI (1.28, 12.48)], stigma [AOR = 2.69; 95% CI (1.34, 5.39)], and lack of social/ family support [AOR = 3.61; 95% CI (1.80, 7.24)] were found to have statistically significant association with an increased odds of MDD; while regular exercise and ever formal counselling were found to have statistically significant association with a decreased odds of MDD. CONCLUSION: The prevalence of MDD among neurolathyrism patients in Dawunt district was high. Lack of social support, stigma, not getting formal counselling, and not involving in regular exercise were modifiable risk factors. Therefore, social support, reducing stigma, formal counselling, and encouraging regular exercise might help to reduce the burden of MDD among neurolathyrism patients.

Prevalence of Neurolathyrism and its associated factors in Grass pea cultivation areas of Dawunt District, North-eastern Ethiopia; 2022: a community based multilevel analysis.

INTRODUCTION: Neurolathyrism is an upper motor neuron disorder characterized by spastic paraparesis, which is caused by the prolonged over-consumption of grass pea. It is a devastating disease with great impacts on physical, social, mental, and economical health. OBJECTIVE: To determine the prevalence of neurolathyrism and its associated factors in grass pea cultivation areas of Dawunt wereda. METHODS: Community based cross-sectional study design was conducted from February 01- March 30, 2021 on 631 Households with a total of 3,350 individuals. Two-stage random sampling technique was used to select participants. Multilevel binary logistic regression was used to identify factors associated with neurolathyrism. Statistical significance was declared at p < 0.05; and AOR with 95% CI was used to interpret the results. RESULTS: The household and population level prevalence of neurolathyrism in Dawunt district were 9.2% (7.2-11.7%) and 2.4% (2.0-2.3.0%) respectively. Age (AOR = 7.4 ( 2.6-20.6)), male sex (AOR = 7.8 (3.9, 15.4)), and marital status (AOR = 4.0 (1.3-12.8)) were the individual level variables; family size (AOR = 12.6 (3.0-52.8)), annual grass pea production (AOR = 5.0 (2.3-11.0)), ever feeding only grass pea (AOR = 8.8(3.5-22.2)), ever feeding immature seeds of grass pea (AOR = 6.28 (2.80, 14.08)), high grass pea to other cereals mixing ratio (> 3:1) (AOR = 6.1 (1.1, 33.5)) were the household level variables found to have significant association with neurolathyrism. CONCLUSION: The prevalence of neurolathyrism was found to be high. Ever feeding only grass pea, Grass pea to other cereals mixing ratio (using ratio of 1:1 or more), and Ever feeding immature grass pea seeds were the modifiable risk factors for neurolathyrism.

Lathyrism in Spain: Lessons from 68 publications following the 1936-39 Civil War.

After the end of the Spanish Civil War (1936-1939), an estimated 1,000 patients presented with lathyrism due to their excessive and prolonged consumption of grasspea (Lathyrus sativus L.) against the backdrop of poverty, drought, and famine. Based on 68 scientific communications between 1941 and 1962 by qualified medical professionals, the disease emerged in different geographical locations involving selective populations: (1) farmers from extensive areas of central Spain, traditionally producers and consumers of grasspea; (2) immigrants in the industrial belt of Catalonia and in the Basque Country, areas with little or no production of grasspea, which was imported from producing areas; (3) workers in Galicia, an area where the legume is neither produced nor consumed, who were seasonally displaced to high-production areas of grasspea in Castille; and (4) inmates of overcrowded postwar Spanish prisons. Original reports included failed attempts by Carlos Jiménez Díaz (1898-1967) to induce experimental lathyrism, the neuropathology of lathyrism in early stages of the disease in two patients, as reported by Carlos Oliveras de la Riva (1914-2007), and the special susceptibility of children to develop a severe form of lathyrism after relatively brief periods of consumption of the neurotoxic seed of L. sativus. In the Spanish Basque Country, L. cicera L. (aizkol) was cultivated exclusively as animal fodder. Patients who were forced to feed on this plant developed unusual manifestations of lathyrism, such as axial myoclonus and severe neuropsychiatric disorders, unknown in other regions of the country and previously unreported. The postwar epidemic of lathyrism in Spain represents the most extensively studied outbreak of this self-limiting but crippling upper motor neuron disease.

Lathyrism and Socioeconomic Disparities: A Neglected Public Health Problem in Northeast Ethiopia.

Lathyrism is an incurable neurological disorder, resulting from excessive consumption of grass pea (Lathyrus sativus), which clinically manifests as paralysis of lower limbs. Because of the high production of grass peas, a large number of people are expected to be affected by the disease in Northeast Ethiopia. However, there is no comprehensive study that quantified the magnitude of the problem. Therefore, in this study, we determined the prevalence of lathyrism and socioeconomic disparities in Northeast Ethiopia. A community-based cross-sectional study was used which used a quantitative method of data collection from January to February 2019. Data were collected from a total of 2,307 inhabitants in the study area using structured questionnaires. Lathyrism cases were identified using a case definition of symmetrical spastic leg weakness, and subacute or insidious onset, with no sensory deficit, and with a history of grass pea consumption before and at the onset of paralysis. The majority (56.8%) of participants were male, and 34.7% were aged 45 years or older. Overall, the prevalence of lathyrism was 5.5%, and it was higher in males (7.9%) than in females (2.5%). Moreover, the prevalence was higher among farmers (7.0%) than merchants (0.3%), very poor economic status (7.2%) than very rich (1.1%), who produced (9.6%) grass pea than not produced (0.9%), and those who used clay pottery (6.2%) than metal (4.8%) for cooking. The prevalence of lathyrism in Northeast Ethiopia is remarkably high. Therefore, we recommend lathyrism to be among the list of reportable health problems and incorporated in the national routine surveillance system.

Prolonged consumption of grass pea (64 g/Cu/day) along with millets and other cereals causes no neurolathyrism.

Objective: To assess the safe limit of L. sativus (grass pea) consumption along with cereals and millets.Methods: A community-based cross-sectional study was undertaken in three districts (Bilaspur, Durg and Raipur) of Chhattisgarh state. A total of 1500 households (HHs) were surveyed. A total of 360 split grass pea (SGP) samples were collected from all three districts for ?-ODAP analysis. Clinical examination was carried out for symptoms of neurolathyrism. Diet survey was done on 5769 HHs by 24hr recall method. Mean intake of different foods and nutrients were calculated. Based on food frequency questionnaire, HHs were separated into daily consumers of SGP along with its quantity consumed and that never consumed SGP.Results: The study revealed that 30 daily consuming and 89 never consuming HHs, in all the three districts. Daily SGP was consumed at an average of 64 g/Cu/day along with millets, cereals and vegetables. Whereas among the never consumers of SGP, mean intake of vegetables was higher than recommended intakes in addition to pulses. The average ?-ODAP content in SGP was 0.630 g%. The nutritional status of children <5 years and the adults was not significantly different between the daily SGP consumers and never consumers. Households in all the three districts, who consumed the SGP recipes, followed the method of washing, boiling, draining the excess water and cooking the pulse.Discussion: There were no adverse effects observed among daily consumers of grass pea (64 g/CU/day) along with millets, cereals and vegetables.

Neurolathyrism in goat (Capra hircus) kid: Model development.

The present study was undertaken to develop an animal model to study neurolathyrism. For this purpose 24 goat (Capra hircus) kids (new born, 15 days old) were divided into four groups. Group I Control, Group II Low toxin (0.17 g% ß-ODAP containing grass pea), Group III high toxin (0.96 g% ß-ODAP containing grass pea) and Group IV high toxin (0.96 g% ß-ODAP containing grass pea flour (powder) fortified with 5 mg% pure ß-ODAP). The experiment was continued for 3 months. Clinical examination was carried out weekly. Muscle conduction velocity (MCV), nerve conduction velocity (NCV), blood and urinary ß-ODAP, nitrite in blood and cerebrospinal fluid (CSF) examination were performed by standard methods. Clinical examination showed neurolathyrism symptoms in three kids. The abnormal MCV and NCV were observed in all the experimental animals. Blood nitrite, blood and urine ß-ODAP levels were significantly increased in experimental groups. Three kids were affected with neurolathyrism due to consumption of grass pea irrespective of its ß-ODAP content and kid may serve as a neurolathyrism model.

Stress-related over-enhancement of the hypothalamic-pituitary-adrenal axis causes experimental neurolathyrism in rats.

Neurolathyrism is a motor neuron disease that is caused by the overconsumption of grass peas (Lathyrus sativus L.) under stressful conditions. The neuro-excitatory ß-N-oxalyl-L-α,ß-diaminopropionic acid present in grass peas was proposed the causative agent of spastic paraparesis of the legs. Historical reports of neurolathyrism epidemics, studies of neurolathyrism animal models, and in vitro studies on the mechanism of ß-N-oxalyl-L-α,ß-diaminopropionic acid toxicity support the hypothesis that stress increases susceptibility to neurolathyrism. To elucidate the role of stress in neurolathyrism-induced motor dysfunction, we focused on the hypothalamic-pituitary-adrenal axis in a rodent model of neurolathyrism. Our results implicated increased glucocorticoid and neuroinflammation in the motor dysfunction (paraparesis) exhibited by the stress loaded rat models of neurolathyrism.

Historical setting and neuropathology of lathyrism: Insights from the neglected 1944 report by Oliveras de la Riva.

Lathyrism is a central motor system disorder recognized since antiquity resulting from prolonged dietary dependence on the grasspea (Lathyrus sativus). The neuropathology underlying the characteristic spastic paraparesis of lathyrism is sketchy. Described here is a landmark but little-known Spanish-language neuropathological study of two patients with lathyrism of recent onset. Due to erroneous interpretations of Filimonov's influential work in 1926, it was assumed that spastic paraparesis of lathyrism was explained by destruction of Betz's pyramidal cells in the motor cortex. Contrary to present understanding, Betz cells and anterior horn cells were preserved, and pathological findings dominated by myelin loss were largely limited to pyramidal tracts in the lumbar cord. Thickening of the adventitia of capillaries and arterioles, together with proliferation of perivascular astrocytes, was found along the length of the spinal cord. Oliveras de la Riva proposed that the segmental spinal pathology arose because distal regions of elongate pyramidal tract axons are distant from their trophic center in the motor cortex, a view not far from the current distal axonopathy concept of lathyrism. In addition, we review the historical circumstances of Filimonov's work in Russia, a summary of the epidemic of lathyrism in Spain following its Civil War (1936-1939), and some historical aspects of the Cajal Institute in Madrid, where Oliveras de la Riva's work was carried out under the supervision of Fernando de Castro, one of Cajal's favorite students.

[Research in Motor Neuron Diseases Caused by Natural Substances: Focus on Pathological Mechanisms of Neurolathyrism].

Diseases of the motor-conducting system that cause moving disability affect socio-economic activity as well as human dignity. Neurolathyrism, konzo, and amyotrophic lateral sclerosis-parkinsonism-dementia complex (ALS-PDC) have attracted researchers to study the pathology of motor neuron (MN) diseases such as ALS. I have been studying neurolathyrism, which is caused by overconsumption of a legume grass pea (Lathyrys sativus L.). Among people who consume the legume as a food staple, many developed life-long paraparesis in their legs. ß-N-oxalyl-l-α,ß- diaminopropionic (l-ß-ODAP; BOAA), contained in this plant, is a neurotoxic analog of l-glutamic acid. We have clarified that in addition to the causal involvement of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) type glutamatergic receptor in MN death, a toxic role of group I metabotropic glutamate receptors as well as transient receptor potential channels were involved in the MN insult by l-ß-ODAP using primary MN culture. We have also established a neurolathyrism rat model by repeated, peripheral l-ß-ODAP treatment to newborn rats under mild stress. Rats showing hind-leg paraparesis with an incidence rate of around 25% were useful to study the in vivo pathology of MN disease. MNs of these rats were greatly decreased at their lumbo/sacral segments at various ages. Intra-parenchymal hemorrhage was consistently observed in paraparetic rats but not in cripple-free, treated rats. MN were depleted even at an acute period around bleeding spots, suggesting catastrophic neuro-vascular-glial interaction in this MN disease. Summaries of konzo and ALS-PDCs studies are also introduced.

Current scenario of consumption of Lathyrus sativus and lathyrism in three districts of Chhattisgarh State, India.

Lathyrism is a disease caused by excessive consumption of grass pea, Lathyrus sativus especially under conditions of severe drought. Grass pea contains 3-N-oxalyl-L-2, 3-diaminopropanoic acid (ß-ODAP) a putative neurotoxin which acts through excitatory mechanism causing Neurolathyrism. Due to awareness of the disease, availability of food and levels of consumption of L. sativus there is reduction in lathyrism cases where higher consumption of L. sativus is reported in India. The present study was undertaken with the objective to assess the current scenario of consumption of L. sativus, incidence of cases of lathyrism, ß-ODAP, protein and amino acids content in L. sativus pulse collected from three districts (Bilaspur, Durg and Raipur) of Chattisgarh state. For this purpose, a total of 17,755 (13,129 rural and 4626 urban) individuals from 151 villages and 60 wards from urban area were covered for clinical examination. Out of total 5769 households (HHs) covered during the survey, 1602 HHs were cultivators, 1791 HHs non-cultivators and 2376 agricultural and other labourers. A one day 24-hour re-call diet survey was carried out in 5758 HHs (4549 rural and 1209 urban). A total of 360 split grass pea (SGP) samples were collected to estimate ß-ODAP, protein and amino acids content. Results of the study revealed that an average consumption of SGP was 20.9 gm/CU/day in Bilaspur and no consumption was reported among urban population of Raipur. Only nine old cases of lathyrism were found during the study. The mean ß-ODAP content in SGP was 0.63 ±â€¯0.14, 0.65 ±â€¯0.13 and 0.65 ±â€¯0.14 gm/100 gm, whereas the protein content was 27.0 ±â€¯2.39, 27.0 ±â€¯1.99 and 26.7 ±â€¯1.90 gm/100 gm in samples collected from Bilaspur, Durg and Raipur districts respectively. Arginine content was high in SGP and sulphur containing amino acids (cysteine and methionine) were less than other amino acids. In conclusion, the consumption of SGP was lower in these three districts with lower ß-ODAP content than earlier reports, thus the lower prevalence of lathyrism in the districts surveyed.

Plant toxin ß-ODAP activates integrin ß1 and focal adhesion: A critical pathway to cause neurolathyrism.

Neurolathyrism is a unique neurodegeneration disease caused by ß-N-oxalyl-L-α, ß- diaminopropionic (ß-ODAP) present in grass pea seed (Lathyrus stativus L.) and its pathogenetic mechanism is unclear. This issue has become a critical restriction to take full advantage of drought-tolerant grass pea as an elite germplasm resource under climate change. We found that, in a human glioma cell line, ß-ODAP treatment decreased mitochondrial membrane potential, leading to outside release and overfall of Ca2+ from mitochondria to cellular matrix. Increased Ca2+ in cellular matrix activated the pathway of ECM, and brought about the overexpression of ß1 integrin on cytomembrane surface and the phosphorylation of focal adhesion kinase (FAK). The formation of high concentration of FA units on the cell microfilaments further induced overexpression of paxillin, and then inhibited cytoskeleton polymerization. This phenomenon turned to cause serious cell microfilaments distortion and ultimately cytoskeleton collapse. We also conducted qRT-PCR verification on RNA-sequence data using 8 randomly chosen genes of pathway enrichment, and confirmed that the data was statistically reliable. For the first time, we proposed a relatively complete signal pathway to neurolathyrism. This work would help open a new window to cure neurolathyrism, and fully utilize grass pea germplasm resource under climate change.

Azañón's disease. A 19th century epidemic of neurolathyrism in Spain.

The cultivation and consumption of grasspea (Lathyrus sativus) in Spain probably dates back centuries, especially during times of famine when the neurotoxic potential of this legume was expressed in the form of a spastic paraparesis known as neurolathyrism. Little known outside the country, the epidemic of neurolathyrism in the years following the Spanish Civil War (1936-1939) came to affect more than a thousand people. In late 1872, during the Six Years Revolutionary Term, young Alejandro San Martín Satrústegui (1847-1908), then editor of the popular weekly El Siglo Médico, travelled to Azañón, a remote village in the province of Guadalajara, to clarify a so-far unknown disease. We analysed the original article published in 1873 by San Martin, as well as communications sent by El Siglo Médico readers reporting similar cases in many other Castilian provinces. San Martín's neurological findings in seven personally examined cases were astonishingly accurate; he concluded the subjects' neurological deficits resulted from injury to the lateral columns in the lower portion of the spinal cord. Description of the clinical findings provided both by San Martín, and by the readers of El Siglo Médico, leave no doubt as to the diagnosis of neurolathyrism. However, none suspected the patient's staple food was the determinant cause of the disease. San Martín proposed the eponym Azañón's disease for lack of a better name the same year (1873) in which Cantani in Italy introduced the term lathyrism. The epidemic of neurolathyrism that affected many Castilian towns represents one of the best-documented in Europe during the last third of the 19th century.

Using Advanced Imaging Methods to Study Neurolathyrism.

BACKGROUND: Neurolathyrism is a toxic nutritional disorder caused by consumption of the grass pea, Lathyrus sativus. The disease, which manifests as an acute or insidiously evolving spastic paraparesis, continues to occur throughout Africa and Asia. Research on this disease is limited, and to our knowledge no imaging studies of patients with neurolathyrism have been published. OBJECTIVES: To better localize the site of damage in neurolathyrism using advanced imaging methods. METHODS: Three male patients, immigrants from Ethiopia, were included in the study. All had a history of arrested spastic paraparesis that had evolved before their emigration from Ethiopia, and a past history of exposure to grass pea without any other cause. Functional magnetic resonance imaging (fMRI) included simple motor tasks to evaluate cortical motor areas. Anatomic scans included diffusion tensor imaging (DTI) to evaluate the corticospinal tracts. RESULTS: In all patients clear activation was found in motor regions, and the patients' activity pattern was qualitatively similar to that in control sublects. In one patient in whom clinical symptoms were asymmetric, an asymmetric activity pattern in Ml was identified. DTI analysis identified intact corticospinal tracts connecting the pons and the primary motor regions, similar to control subjects. CONCLUSIONS: Advanced neuroimaging clearly identified well-functioning motor regions and tracts in neurolathyrism patients, suggesting a spinal etiology.

Bone fracture toughness and strength correlate with collagen cross-link maturity in a dose-controlled lathyrism mouse model.

Collagen cross-linking is altered in many diseases of bone, and enzymatic collagen cross-links are important to bone quality, as evidenced by losses of strength after lysyl oxidase inhibition (lathyrism). We hypothesized that cross-links also contribute directly to bone fracture toughness. A mouse model of lathyrism using subcutaneous injection of up to 500 mg/kg ß-aminopropionitrile (BAPN) was developed and characterized (60 animals across 4 dosage groups). Three weeks of 150 or 350 mg/kg BAPN treatment in young, growing mice significantly reduced cortical bone fracture toughness, strength, and pyridinoline cross-link content. Ratios reflecting relative cross-link maturity were positive regressors of fracture toughness (HP/[DHLNL + HLNL] r(2) = 0.208, p < 0.05; [HP + LP]/[DHNL + HLNL] r(2) = 0.196, p < 0.1), whereas quantities of mature pyridinoline cross-links were significant positive regressors of tissue strength (lysyl pyridinoline r(2) = 0.159, p = 0.014; hydroxylysyl pyridinoline r(2) = 0.112, p < 0.05). Immature and pyrrole cross-links, which were not significantly reduced by BAPN, did not correlate with mechanical properties. The effect of BAPN treatment on mechanical properties was dose specific, with the greatest impact found at the intermediate (350 mg/kg) dose. Calcein labeling was used to define locations of new bone formation, allowing for the identification of regions of normally cross-linked (preexisting) and BAPN-treated (newly formed, cross-link-deficient) bone. Raman spectroscopy revealed spatial differences attributable to relative tissue age and effects of cross-link inhibition. Newly deposited tissues had lower mineral/matrix, carbonate/phosphate, and Amide I cross-link (matrix maturity) ratios compared with preexisting tissues. BAPN treatment did not affect mineral measures but significantly increased the cross-link (matrix maturity) ratio compared with newly formed control tissue. Our study reveals that spatially localized effects of short-term BAPN cross-link inhibition can alter the whole-bone collagen cross-link profile to a measureable degree, and this cross-link profile correlates with bone fracture toughness and strength. Thus, cross-link profile perturbations associated with bone disease may provide insight into bone mechanical quality and fracture risk.

Determination of ß-N-oxalyl-L-α,ß-diaminopropionic acid and homoarginine in Lathyrus sativus and Lathyrus cicera by capillary zone electrophoresis.

BACKGROUND: Lathyrus species as legumes represent an alternative protein source for human and animal nutrition. Heavy consumption of these species can lead to lathyrism, caused by the non-protein amino acid ß-N-oxalyl-l-α,ß-diaminopropionic acid (ß-ODAP). Currently, there is no well-defined level below which ß-ODAP is considered non-toxic. In this work, the ß-ODAP content was determined in L. sativus and L. cicera samples to assess their potential toxicity. Homoarginine is another non-protein amino acid found in Lathyrus spp. with interesting implications for human and animal nutrition. RESULTS: The level of ß-ODAP found in these two species ranged from 0.79 to 5.05 mg g(-1). The homoarginine content of the samples ranged from 7.49 to 12.44 mg g(-1). CONCLUSION: This paper describes an accurate, fast and sensitive method of simultaneous detection and quantification of ß-ODAP and homoarginine by capillary zone electrophoresis in L. cicera and L. sativus seeds. Moreover, several methods of extraction were compared to determine the highest performance.

Grass pea consumption & present scenario of neurolathyrism in Maharashtra State of India.

BACKGROUND & OBJECTIVES: Neurolathyrism is a non progressive motor neuron disorder engendered by the prolonged over-consumption of Lathyrus sativus (grass pea) seeds which contain a neurotoxic amino acid, ß-N oxalyl- L-α, ß-diaminopropionic acid (ß-ODAP). It is characterized by spastic paraparesis in the hind limbs. The present study was conducted in 105 households (HHs) of Gondia district in Maharashtra, India, where grass pea is cultivated and consumed to assess the health implication of its consumption. METHODS: Across-sectional survey was carried out in 105 HHS in five villages and grass pea samples were collected for ß-ODAP estimation. Amino acid analysis was also done, neurolathyrism cases were identified by snowball sampling method and neurological examination was carried out. RESULTS: The study revealed that 61 per cent of population was consuming this pulse as a part of diet. ß-ODAP concentration in grass pea was high in Bora village (1254.5 ± 528.21 mg %) and less in Malgaon village (413.6±415.79 mg %). The nutritional status of the people was within the normal range (BMI 18± 3.40 kg/m2) in the surveyed households. Consumption of grass pea was observed to be less than 25 g. CONCLUSIONS: The cases of neurolathyrism declined in all the studied villages due to reduced ß-ODAP exposure through Lathyrus sativus consumption, however, the grass pea was cultivated and consumed in Gondia district of Maharashtra State.

New insights into the mechanism of neurolathyrism: L-ß-ODAP triggers [Ca2+]i accumulation and cell death in primary motor neurons through transient receptor potential channels and metabotropic glutamate receptors.

Neurolathyrism is a motor neuron (MN) disease caused by ß-N-oxalyl-L-α,ß-diaminopropionic acid (L-ß-ODAP), an AMPA receptor agonist. L-ß-ODAP caused a prolonged rise of intracellular Ca(2+) ([Ca(2+)]i) in rat spinal cord MNs, and the [Ca(2+)]i accumulation was inversely proportional to the MN's life span. The [Ca(2+)]i rise induced by L-ß-ODAP or (S)-AMPA was antagonized completely by NBQX, an AMPA-receptor blocker. However, blocking the L-type Ca(2+) channel with nifedipine significantly lowered [Ca(2+)]i induced by (S)-AMPA, but not that by L-ß-ODAP. Tetrodotoxin completely extinguished the [Ca(2+)]i rise induced by (S)-AMPA or kainic acid, whereas that induced by L-ß-ODAP was only attenuated by 65.6±6% indicating the prominent involvement of voltage-independent Ca(2+) entry. The tetrodotoxin-resistant [Ca(2+)]i induced by L-ß-ODAP was blocked by 2-APB, Gd(3+), La(3+), 1-(ß-[3-(4-methoxy-phenyl)propoxy]-4-methoxyphenethyl)-1H-imidazole hydrochloride (SKF-96365) and flufenamic acid, which all are blockers of the transient receptor potential (TRP) channels. Blockers of group I metabotropic glutamate receptors (mGluR I), 7-(hydroxyiminocyclopropan[b]chromen-1α-carboxylate ethyl ester (CPCCPEt) and 2-methyl-6-(phenylethynyl)-pyridine (MPEP) also lowered the [Ca(2+)]i rise by L-ß-ODAP. MN cell death induced by L-ß-ODAP was prolonged significantly with SKF-96365 as well as NBQX. The results show the involvement of TRPs and mGluR I in L-ß-ODAP-induced MN toxicity through prolonged [Ca(2+)]i mobilization, a unique characteristic of this neurotoxin.