Enteric nervous system and inflammatory bowel diseases: Correlated impacts and therapeutic approaches through the P2X7 receptor

Table 1 Specific variations in cell number and neuronal profile area according to the respective chemical code observed in the submucosal plexus of the enteric nervous system

Ref.	Species	Colitis	Time	Submucosal plexus
				Cellular chemical code (change in density compared to healthy tissues, %)	Cellular chemical code (change in profile area compared to healthy tissues, %)
Schneider et al[169]	Human	Crohn’s disease	6.1±6,3 years	ChAT, nNOS, SP, and NSE (similar to); VIP (> 16%-CT)	N/A
Sigalet et al[170]	Rat	TNBS-50% ethanol	5 d	PGP9.5 (<)1; VIP (<)1; S100 β (<)1	N/A
da Silva et al[130]	Rat	TNBS-30% ethanol	24 h	P2X7 (< 21%-CT; < 13%-sham) ; Calret (< 11.7%-CT; < 8%-sham); Calb (< 34%-CT; < 30%-sham); HuC/D (< 33.4%-CT; < 28%sham); S100β (< 44.2%-CT; < 33%-sham)	Calbindin (< 25%-CT/sham)

¹Count change without percentage information.

TNBS: 2,4,6-trinitrobenzenesulfonic acid; N/A: Not applicable; (<): Cell count/area decreased; (>): Cell count/area increased; ir: immunoreactive; CT: Control group; Sham: Sham group; P2X7: P2X7 receptor; ChAT: Acetylcholine transferase enzyme-ir; nNOS: Neuronal nitric oxide synthase enzyme-ir; Calret: Calretinin-ir; Calb: Calbindin-ir; SP: Substance P-ir; VIP: Vasoactive intestinal polypeptide-ir; HuC/D and PGP9. 5: Pan neuronal-ir; NSE: Neuron-specific enolase-ir; S100β: Protein β for calcium S100-ir labeling.

Table 2 Specific variations in cell number and neuronal profile area according to the respective chemical code observed in the myenteric plexus of the enteric nervous system

Ref.	Species	Colitis	Time	Myenteric plexus
				Cellular chemical code (change in density compared to healthy tissues, %)	Cellular chemical code (change in profile area compared to healthy tissues, %)
Boyer et al[79]	Mice	DNBS-50% ethanol	0.5 - 120 h	HuC/D (< 42%-CT)	N/A
Linden et al[17]	Guinea pig	TNBS-30% ethanol	2 - 12 h;1-56 d	HuC/D 12 and 24 h (< 15%-CT); HuC/D 6 and 56 d (< 20%-CT); ChAT, nNOS, calret and NeuN 6 d (=); VIP 6 (>)1 and 56 d (No differences)	N/A
Sarnelli et al[171]	Rat	TNBS-50% ethanol	7 d	HuC/D (< 20%-CT)	N/A
Gulbransen et al[19]	Mice	DNBS-50% ethanol	48 h	HuC/D (< 32%-CT)	N/A
Linden[77]	Guinea pig	TNBS-30% ethanol	24 h	HuC/D (< approximately 20%-25%-CT)	N/A
Da Silva et al[129]	Rat	TNBS-30% ethanol	24 h	P2X7 (< 11%-CT); ChAT (< 34.9%-CT); nNOS (< 42.3%-CT; < 18%-sham); Calret (< 60.6%-CT; < 15%-sham); Calbindin (< 22.9%-CT); HuC/D (< 33.3%-CT; < 16%-sham); S100β (< 29.2%-CT; < 23%-sham)	nNOS (< 6.6%-CT/sham); ChAT (< 21.2%-CT/sham); Calbindin (>19%-CT); Calretinin (< 2%-sham)
Souza et al[133],2	Rat	TNBS-30% ethanol	24 h	P2X7 (< 10.6%-sham; < 20.4%-BBG); ChAT (< 34%-sham; < 13.9%-BBG); nNOS (< 22.9%-sham; < 22.2%-BBG); HuC/D (< 15.4%-sham; < 19.5%-BBG); GFAP (< 14.4%-sham; < 17.7%-BBG)	nNOS (< 12%-sham; < 8%-BBG); ChAT and HuC/D (No differences)

¹Change in count without percentage information.

²Data from ileum after colitis. DNBS: Dinitrobenzene sulfonic acid; TNBS: 2,4,6-trinitrobenzenesulfonic acid; N/A: Not applicable; (=): Similarity of cell count; (<): Cell count/area decrease; (>): Cell count/area increase; ir: Immunoreactive; CT: Control group; Sham: Sham group; BBG: Brilliant Blue G-treated animals group; P2X7: P2X7 receptor; ChAT: Acetylcholine transferase enzyme-ir; nNOS: Neuronal nitric oxide synthase enzyme-ir; Calret: Calretinin-ir; VIP: Vasoactive intestinal polypeptide-ir; HuC/D: Neuronal pan-ir; NeuN: Neuronal nuclear antigen-ir; GFAP: Glial fibrillary acid protein-ir; S100β: Protein β for calcium S100-ir labeling.

Table 3 Specific distribution of the P2X7 receptor in relation to cells with different chemical code that integrate the enteric nervous system

Ref.	Species	Tissue	Chemical cellular code (p2x7 receptor expression, %)
			Submucosal plexus	Myenteric plexus
Hu et al[125]	Guinea pig	Ileum	ChAT, calret, NPY and SP	nNos, calret, calb, NPY, SP, and HuC/D
Hu et al[125]	Guinea pig	Stomach and intestines	N/A	nNos, calret, calb, NPY, SP, and HuC/D
Vanderwinden et al[126]	Rat	Stomach, jejunum, and colon	S100β	S100β
Gulbransen et al[19]	Human and mice	Colon	+	+
Girotti et al[121]	Rat	Large intestine	P2X7 in 100% of ChAT, calret, and calb; ChAT (22.5%), calret (35%) and calb (12.7%)	P2X7 in 100% of ChAT, nNOS, calret, and calb; ChAT (12.7%), nNOS (35.7%), calret (17.6%) and calb (8.3%)
Palombit et al[127]	Rat	Ileum	N/A	P2X7 in 100% of ChAT, nNOS, calret, and calb; ChAT (42.2%), nNOS (24.5%), calret (33.5%), and calb (10.7%)
Antonioli et al[128]	Rat	Distal colon	N/A	P2X7 in 100% of HuC/D
Da Silva et al[129]	Rat	Distal colon	N/A	P2X7 in 100% of ChAT, nNOS, calret, calb, and S100β
Da Silva et al[130]	Rat	Distal colon	P2X7 in 100% of calret, calb, HuC/D, and S100β	N/A

(+): P2X7 receptor positivity without cellular chemical code information; N/A: Not applicable; ir: Immunoreactive; ChAT: Acetylcholine transferase enzyme-ir; nNOS: Neuronal nitric oxide synthase enzyme-ir; Calret: Calretinin-ir; Calb: Calbindin-ir; NPY: Neuropeptide Y-ir; SP: Substance P-ir; HuC/D: Neuronal pan-ir; NF200: Neurofilament 200-ir; GFAP: Glial fibrillary acid protein-ir; S100β: Protein β for calcium S100-ir labeling.