Synergistic Action of Paraquat and Lectins in the Development of Parkinsonian‐like Gastric Dysmotility
Authors: Skolka Michael Paul , Anselmi Laura , Travagli R. Alberto 
Published: November 2023

Parkinson's disease (PD) is a neurodegenerative disorder of dopaminergic neurons of the substantia nigra pars compacta (SNpc) characterized by motor symptoms and non‐motor effects, such as gastrointestinal (GI) dysmotility. In recent years, idiopatic PD has been hypothesized to be triggered by the passage of environmental pathogens through the wall of the GI tract; these pathogens then travel retrogradely to the central nervous system via the vagus nerve, and induce the degeneration of dopaminergic neurons typical of PD.

We have shown previously that ingestion of high doses of lectins (0.2%) reduces gastric motility in a manner reminiscent of the gastric dysfunctions observed in PD patients, thus suggesting that lectins may either be the environmental pathogen themselves or may facilitate the transport to the CNS of toxins known to cause PD. One of these toxins is the herbicide paraquat, which, when administered at high doses (up to 100mg/kg), induces degeneration of dopaminergic neurons and PD‐like motor symptoms.

In the present work we aimed to test the hypothesis that gastric administration of low doses of lectins and paraquat, at concentrations that by themselves would not induce any gastric dysfunction, induce gastric dysmotilty.

Six rat groups were gavaged with 200μl for 7 days with i) 1% sucrose; ii) 0.5% lectin from Pisum Sativum; iii–iv) paraquat, 1 or 5mg/kg; v–vi) lectins + paraquat, 1 or 5mg/kg. In order to test the hypothesis a vagal transport of the toxins and test motor dysfunctions, the posterior sub‐diaphragmatic vagal branch was sectioned three days prior to gavage. Motor behavior, and gastric motility/tone were measured seven days post‐gavage via strain gauges sewn to the anterior gastric surface.

Motor behavioral tests (vibrissae, stepping and apomorphine tests) did not reveal any motor dysfunction in any of the tested rats.

Brainstem microinjection of TRH was used to activate vagal efferent motorneurons and increase tone and motility (N=3–4 for each data point)

Antrum Tone (mg)
Antrum Motility (% of baseline)

TRH
0.1 pmol
1 pmol
3 pmol
0.1 pmol
1 pmol
3pmol

Control
289±23
1102±52
1354±83
226±61
319±31
420±20

Lectin 0.05%
159±29
1152±34
1371±111
238±12
250±50
386±43

Paraquat 1mg/kg
130±21
683±98
815±103
202±16
301±40
367±17

Paraquat 5 mg/kg
0**
150±19**
188±17**
95±4*
164±23*
275±25*

Lectin + Paraquat 1mg/kg
9±9**
198±60**
329±128**
107±4*
215±30*
264±50*

Lectin + Paraquat 5 mg/kg
0**
147±35**
181±46**
106±12*
209±55**
240±60**

Corpus Tone (mg)
Corpus Motility (% of baseline)

TRH
0.1 pmol
1 pmol
3 pmol
0.1 pmol
1 pmol
3pmol

Control
178±74
230±29
398±16
251±36
251±21
360±17

Lectin 0.05%
103±5
183±37
327±9
238±12
250±50
385±42

Paraquat 1mg/kg
129±14
232±13
369±9
202±16
301±40
367±17

Paraquat 5 mg/kg
0*
163±35
281±54*
95±4*
164±22*
275±25*

Lectin + Paraquat 1mg/kg
20±20*
180±15*
252±39*
107±4*
186±13*
264±50*

Lectin + Paraquat 5 mg/kg
0*
113±7*
237±45*
106±11*
157±46*
240±60*

P<0.05

P<0.01

The decreased response to TRH observed in rats gavaged with paraquat and/or lectins was no due to gastric smooth muscle dysfunction since similar responses were observed in all groups upon i.p. injection of the muscarinic agonist bethanecol, which activates gastric muscle cells directly (n=3 per each group).

These data suggest lectins enhanced the low dose paraquat's ability to cause GI dysmotility and may be implicated in gastric‐related PD's etiology.

Support or Funding Information

Grant support from the Parkinson's Disease Foundation and NIH DK 55530